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1.
Acta Pharmaceutica Sinica ; (12): 455-463, 2024.
Article in Chinese | WPRIM | ID: wpr-1016654

ABSTRACT

Thrombus is a major factor leading to cardiovascular diseases such as myocardial infarction and stroke. Although fibrinolytic anti-thrombotic drugs have been widely used in clinical practice, they are still limited by narrow therapeutic windows, short half-lives, susceptibility to inactivation, and abnormal bleeding caused by non-targeting. Therefore, it is crucial to effectively deliver thrombolytic agents to the site of thrombus with minimal adverse effects. Based on the long blood circulation and excellent drug-loading properties of human serum albumin (HSA), we employed genetic engineering techniques to insert a functional peptide (P-selectin binding peptide, PBP) which can target the thrombus site to the N-terminus of HSA. The fusion protein was expressed using Pichia pastoris and purified by Ni-chelating affinity chromatography. After being loaded with gold nanoparticles (Au NPs), the fusion protein formed homogeneous and stable nanoparticles (named as PBP-HSA@Au) with a diameter of 17.7 ± 1.0 nm and a zeta potential of -11.3 ± 0.2 mV. Cytotoxicity and hemolysis tests demonstrated the superb biocompatibility of PBP-HSA@Au. Platelet-targeting experiments confirmed the thrombus-targeting ability conferred by the introduction of PBP into PBP-HSA@Au. Upon near-infrared ray (NIR) irradiation, PBP-HSA@Au rapidly converted light energy into heat, thereby disrupting fibrinogen and exhibiting outstanding thrombolytic efficacy. The designed HSA fusion protein delivery system provides a precise, rapid, and drug-free treatment strategy for thrombus therapy. This system is characterized by its simple design, high biocompatibility, and strong clinical applicability. All animal experiments involved in this study were carried out under the protocols approved by the Animal Experiment Ethics Committee of Jiangnan University [JN. No20230915S0301015(423)].

2.
Acta Pharmaceutica Sinica B ; (6): 3471-3488, 2023.
Article in English | WPRIM | ID: wpr-1011111

ABSTRACT

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

3.
Acta Pharmaceutica Sinica ; (12): 274-284, 2023.
Article in Chinese | WPRIM | ID: wpr-965709

ABSTRACT

Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.

4.
Acta Pharmaceutica Sinica ; (12): 560-570, 2023.
Article in Chinese | WPRIM | ID: wpr-965640

ABSTRACT

The active ingredient of traditional Chinese medicine, silybin (SBN), can inhibit the proliferation of cancer cells and enhance the anticancer effect of doxorubicin (DOX). However, due to non-targeting and short half-life of SBN and DOX, as well as different administration routes and pharmacokinetic processes, this combination drug cannot act on the tumor in the set order, seriously eliminating the synergistic effect between them and limiting the effect in vivo. Therefore, we intended to construct a nano-delivery system based on molybdenum disulfide (MoS2), modified by polyethylene glycol (PEG) and sialic acid (SA), and co-loaded with SBN and DOX. The system induced the release of combined drugs under the dual-stimulation of pH and near infra-red (NIR), increased the free concentration of intracellular drugs, so as to achieve the synergistic effect between them. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Fujian University of Traditional Chinese Medicine. MoS2-PEG-SA-SBN/DOX circulated in vivo, and effectively accumulated at tumor sites through enhanced permeability and retention effect (EPR) and SA-mediated active targeting. Under near infrared light irradiation, MoS2-PEG-SA-SBN/DOX realized the combination of synergistic chemotherapy and photothermal therapy for tumor, thus achieving excellent anti-tumor effect in vivo. This study can provide a new idea and strategy for the clinical treatment of lung cancer. Taken together, MoS2-PEG-SA-SBN/DOX can offer a new idea and strategy for the clinical treatment of lung cancer.

5.
Acta Pharmaceutica Sinica ; (12): 506-515, 2023.
Article in Chinese | WPRIM | ID: wpr-965613

ABSTRACT

Exosome is a self-secreted phospholipid bilayer nanovesicles, and has shown great potential in drug delivery field due to the important advantages of low immunogenicity and homologous targeting. Phototherapy, mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT), utilize light to activate photoactive drug for tumor cell killing. The advanced therapeutic strategy shows low toxic side-effect and non-invasion precise advantages, and thus has made great progress in tumor treatment over the past few years. Therefore, using exosomes as a drug delivery system to deliver phototherapeutic agents can improve therapeutic performances with a reduced side-effect, and further enhance their application potential for clinical tumor therapy. This review focus on the rising cross-subjects field involving exosomes and phototherapy, and mainly introduce the research progress and relative case of exosomes-based delivery system for cancer phototherapy. Additionally, the advantages and challenges of exosome-based phototherapy are also discussed and proposed.

6.
Acta Pharmaceutica Sinica B ; (6): 863-878, 2023.
Article in English | WPRIM | ID: wpr-971715

ABSTRACT

Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD4)-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe3+/Fe2+) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both in vitro and in vivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD4-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.

7.
Acta Pharmaceutica Sinica B ; (6): 284-297, 2023.
Article in English | WPRIM | ID: wpr-971682

ABSTRACT

Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds. Photothermal therapy (PTT) emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat. However, the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues. Besides, the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation. Herein, we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds. Gelatin was used as inner layer hydrogel to reserve lysozyme (LZM) loaded mesoporous polydopamine (MPDA) (MPDA-LZM) nanoparticles, which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles. MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability, could deeply penetrate and destroy biofilms. In addition, the outer layer hydrogel consisted of gelatin methacryloyl (GelMA) and epidermal growth factor (EGF) promoted wound healing and tissue regeneration. It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo. Overall, the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds.

8.
China Pharmacy ; (12): 1781-1787, 2023.
Article in Chinese | WPRIM | ID: wpr-978975

ABSTRACT

As an adjuvant alternative therapy, phototherapy is widely used for early diagnosis and late treatment of breast cancer due to its non-invasive treatment characteristics. But the application of phototherapeutic agents has been limited in the clinic due to poor hydrophobicity and tissue targeting, low photostability, and obvious toxic side effects in vivo. With the development of nanotechnology, new composite nano-phototherapy agents have emerged. This paper summarizes the latest developments and findings of new composite nano-phototherapy agents for phototherapy in the field of breast cancer treatment in the past 5 years. With the development of multifunctional nanomaterials in the field of breast cancer imaging diagnosis and treatment, the modified phototherapy agent achieved further development respectively from improving light response to improve the light thermal conversion or increasing the generation of reactive oxygen species, targeting tumor microenvironment, immune cells and cancer cell surface receptors to achieve drug controllable response release, using biomimetic materials and endogenous substances to improve biocompatibility. Although phototherapeutic agents exhibit high cell-killing rates in the treatment of metastatic breast cancer models and effectively inhibit their recurrence and metastasis, problems remain regarding the safety and compatibility of synergistic therapy. Future studies can not only improve the existing effects of phototherapeutic agents, but also develop oral drugs with more convenient routes based on immunotherapy to amplify the immune response and resist breast cancer through multiple routes.

9.
Chinese Journal of Reparative and Reconstructive Surgery ; (12): 1444-1450, 2023.
Article in Chinese | WPRIM | ID: wpr-1009081

ABSTRACT

OBJECTIVE@#The research progress of new multifunctional bone cement in bone tumor therapy in recent years was reviewed, in order to provide help for the future research of anti-tumor bone cement.@*METHODS@#The related literature on the treatment of bone tumors with new multifunctional bone cement at home and abroad in recent years was extensively reviewed and summarized.@*RESULTS@#The new multifunctional bone cements include those with the functions of photothermotherapy, magnetic thermotherapy, chemoradiotherapy, and antibacterial after operation, which are discussed from the aspects of anti-tumor, drug controlled release, and cytotoxicity. Controlled drug release has been achieved in multifunctional bone cements by adjusting heat and pH or incorporating particles such as chitosan oligosaccharides and γ-cyclodextrin. At present, multifunctional bone cement with hyperthermia, radiotherapy, and chemotherapy has effectively inhibited the local recurrence and distant metastasis of bone tumors. Broadening the application of bone cement for photothermal and magnetic thermal therapy to deeper bone tumors, investigating more precise controlled release of drug-loaded bone cement, and introducing nanoparticles with both thermal conversion and intrinsic enzymatic activities into bone cement for synergistic anti-tumor therapy are promising research directions.@*CONCLUSION@#The new multifunctional bone cement inhibits bone tumor cells, promotes new bone formation in bone defects, and prevents incision infection after tumor resection. Certain progress has been made in anti-tumor, antibacterial, drug-controlled release, and reduction of cytotoxicity. Expanding the deeper application range of the new multifunctional bone cement, verifying the safety in clinical application, and focusing on the individualized treatment of the new multifunctional bone cement are the problems that need to be solved in the future.


Subject(s)
Humans , Bone Cements/therapeutic use , Delayed-Action Preparations , Bone Neoplasms/therapy , Anti-Bacterial Agents/therapeutic use , Nanoparticles/therapeutic use
10.
Chinese Journal of Reparative and Reconstructive Surgery ; (12): 937-944, 2023.
Article in Chinese | WPRIM | ID: wpr-1009005

ABSTRACT

OBJECTIVE@#To design and construct a graphene oxide (GO)/silver nitrate (Ag3PO4)/chitosan (CS) composite coating for rapidly killing bacteria and preventing postoperative infection in implant surgery.@*METHODS@#GO/Ag3PO4 composites were prepared by ion exchange method, and CS and GO/Ag3PO4 composites were deposited on medical titanium (Ti) sheets successively. The morphology, physical image, photothermal and photocatalytic ability, antibacterial ability, and adhesion to the matrix of the materials were characterized.@*RESULTS@#The GO/Ag3PO4 composites were successfully prepared by ion exchange method and the heterogeneous structure of GO/Ag3PO4 was proved by morphology phase test. The heterogeneous structure formed by Ag3PO4 and GO reduced the band gap from 1.79 eV to 1.39 eV which could be excited by 808 nm near-infrared light. The photothermal and photocatalytic experiments proved that the GO/Ag3PO4/CS coating had excellent photothermal and photodynamic properties. In vitro antibacterial experiments showed that the antibacterial rate of the GO/Ag3PO4/CS composite coating against Staphylococcus aureus reached 99.81% after 20 minutes irradiation with 808 nm near-infrared light. At the same time, the composite coating had excellent light stability, which could provide stable and sustained antibacterial effect.@*CONCLUSION@#GO/Ag3PO4/CS coating can be excited by 808 nm near infrared light to produce reactive oxygen species, which has excellent antibacterial activity under light.


Subject(s)
Chitosan , Silver Nitrate , Titanium , Anti-Bacterial Agents/pharmacology , Coloring Agents
11.
China Journal of Chinese Materia Medica ; (24): 4981-4992, 2023.
Article in Chinese | WPRIM | ID: wpr-1008668

ABSTRACT

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.


Subject(s)
Humans , Animals , Mice , Photothermal Therapy , Triple Negative Breast Neoplasms/pathology , Antimicrobial Cationic Peptides , Immunotherapy/methods , Cell Line, Tumor , Phototherapy/methods , Nanoparticles/chemistry
12.
Acta Pharmaceutica Sinica B ; (6): 2346-2368, 2023.
Article in English | WPRIM | ID: wpr-982862

ABSTRACT

Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control, light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.

13.
Acta Pharmaceutica Sinica B ; (6): 1903-1918, 2023.
Article in English | WPRIM | ID: wpr-982834

ABSTRACT

Interaction between tumour cells and macrophages enables cancer cells to evade immune detection and clearance by interfering with macrophage phagocytosis. The anti-phagocytic signals regulated by anti-phagocytic proteins are termed "don't eat me" signals; these signals include sialic acid-binding immunoglobulin-type lectin-10 (Siglec-10) and the recently revealed CD24 immune checkpoint (ICP). In this study, we demonstrate that targeting a specific glycan on CD24 exhibits the potential to inhibit ICP. Sambucus nigra agglutinin (SNA), a sialic acid-binding lectin, was employed to block CD24 and to enhance phagocytosis in melanoma tumours. In addition, we prepared SNA-conjugated hollow gold-iron oxide nanoparticles for photothermal therapy of tumours. Our findings show that the combination treatment of SNA-conjugated photothermal nanoparticles and near-infrared exposure successfully augments tumour cell phagocytosis both in vitro and in vivo models.

14.
Acta Pharmaceutica Sinica ; (12): 2794-2801, 2023.
Article in Chinese | WPRIM | ID: wpr-999018

ABSTRACT

Diabetic ulcer is recognized as a chronic nonhealing wound, often associated with bacterial infection and tissue necrosis, which seriously affect patients' health and quality of life. The traditional treatment methods exist some problems, such as bacterial resistance and secondary trauma, so it is urgent to find new methods to meet the requirements of diabetic ulcer treatment. In this study, we prepared a drug delivery system (DFO@CuS nanoparticles) based on hollow copper sulfide (CuS) nanoparticles loaded with deferoxamine (DFO), which realized the synergistic therapy of promoting angiogenesis and photothermal antibacterial. The morphological structure and particle size distribution of DFO@CuS nanoparticles were characterized by transmission electron microscopy and particle size analyzer, respectively. The antibacterial effect of DFO@CuS nanoparticles was evaluated by the plate coating method. The effects of DFO@CuS nanoparticles on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8 (cell counting kit-8) assay, cell scratch assay, and tube formation assay. The results showed that DFO@CuS nanoparticles were hollow and spherical in shape with an average particle size of (200.9 ± 8.6) nm. DFO@CuS nanoparticles could effectively inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) under near-infrared (NIR) light irradiation. DFO@CuS nanoparticles showed negligible cytotoxicity and effective acceleration of cell migration and tube formation in a certain concentration range. In conclusion, the prepared DFO@CuS nanoparticles exhibit good photothermal antibacterial properties and pro-angiogenic effects, providing a basis for their application in the treatment of diabetic ulcer.

15.
International Journal of Biomedical Engineering ; (6): 36-41, 2023.
Article in Chinese | WPRIM | ID: wpr-989313

ABSTRACT

Objective:To establish a method for preparing ferritin-Prussian blue nanocomposites (ferritin-PB NPs) and evaluate their photothermal conversion performance and photothermally responsive tumor cell killing effect.Methods:Prussian blue nanomaterials were prepared by the precipitation method and then loaded into the ferritin cavity to construct ferritin-PB NPs. The composition of ferritin-PB NPs was tested by infrared spectroscopy and UV-vis absorption spectroscopy. The size and morphology of ferritin-PB NPs were measured by dynamic light scattering and transmission electron microscopy. The photothermal heating effect and photothermal stability effect of the ferritin-PB NPs material were tested by a thermal imager. The uptake effect of ferritin-PB NPs in HeLa and HepG2 tumor cells was observed by laser confocal microscopy. The photothermal killing effect of ferritin-PB NPs on HeLa tumor cells was tested by the MTT assay.Results:The morphology of the ferritin-PB NPs is a composite structure of ferritin coated with PB NPs, which can rapidly convert light energy into heat energy in response to 730 nm laser irradiation, resulting in a significant increase in the temperature of the test solution. The ferritin-PB NPs were rapidly taken up by HeLa and HepG2 tumor cells and significantly inhibited the proliferation of HeLa cells under 730 nm light irradiation.Conclusions:The ferritin-PB NPs were obtained by a simple preparation method, which has good biocompatibility and photothermal cytotoxicity and is expected to be used for in vivo tumor therapy in the extended research.

16.
Acta Pharmaceutica Sinica ; (12): 211-221, 2022.
Article in Chinese | WPRIM | ID: wpr-913173

ABSTRACT

Photothermal therapy (PTT) is a highly effective anti-tumor method. However, when laser radiation was used to ablate tumors, it usually triggers a series of inflammatory reactions, promoting the further development of tumors and affecting the effect of anti-tumor therapy. Therefore, it is an effective method to improve the anti-tumor effect by suppressing the inflammatory response through the precise targeted delivery of anti-inflammatory drug while realizing the photothermal treatment of tumors. To this end, the redox-responsive linker 3,3'-dithiodipropionic acid was used to bond the classic hydrophobic anti-inflammatory drug 18β-glycyrrhetinic acid (18β-GA) and the hydrophilic fragment methoxy-polyethylene glycol (mPEG-NH2) to obtain redox-responsive amphiphilic polymer PEG-DA-GA in this study. Then, photothermal agent IR-780 was encapsulated to prepare redox-responsive polymer micelle PDG/IR-780 NPs. The PDG/IR-780 NPs exhibited uniform particle size of 80.2 ± 5.3 nm and the polydispersity index (PDI) was 0.215 ± 0.079. All animal experiments followed the ethical requirements formulated by the Ethics Committee of Sichuan University. The results showed that PDG/IR-780 NPs could respond to the abundant glutathione (GSH) in tumor cells to promote the disintegration of nanoparticle and the release of 18β-GA, thus significantly improved the killing efficiency on 4T1 cells, when compared with the non-redox-responsive control PSG/IR-780 NPs. When the concentration of 18β-GA was 50 μg·mL-1, the cell viability of 4T1 cells in the PDG/IR-780 NPs group was only (19.29 ± 1.80) %, which was significantly lower than the result of in PSG/IR-780 NPs group (29.30 ± 1.37) %. The results of frozen sections of tumor tissues showed that the designed PDG NPs can promote the tumor-targeted distribution of drugs compared with the free drug group. Eventually, PDG/IR-780 NPs achieved wonderful anti-tumor efficacy on 4T1 triple-negative breast cancer model, revealing the new possibility of the combined therapy strategy of photothermal and anti-inflammatory therapy.

17.
Acta Pharmaceutica Sinica B ; (6): 107-134, 2022.
Article in English | WPRIM | ID: wpr-929284

ABSTRACT

The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.

18.
Journal of Biomedical Engineering ; (6): 398-404, 2022.
Article in Chinese | WPRIM | ID: wpr-928237

ABSTRACT

This study aims to explore the potential of polyaspartic acid grafted dopamine copolymer (PAsp- g-DA) chelated Fe 3+ for magnetic resonance imaging (MRI) visual photothermal therapy. Polyaspartic acid grafted copolymer of covalently grafted dopamine and polyethylene glycol (PAsp- g-DA/PEG) was obtained by the ammonolysis reaction of poly succinimide (PSI), and then chelated with Fe 3+ in aqueous solution. The relaxivity in vitro, magnetic resonance imaging enhancement in vivo and photothermal conversion effect at 808 nm were investigated. The results showed that polymeric iron coordination had good near-infrared absorption and photothermal conversion properties, good magnetic resonance enhancement effect, and good longitudinal relaxation efficiency under different magnetic field intensities. In summary, this study provides a new magnetic resonance visual photothermal therapeutic agent and a new research idea for the research in related fields.


Subject(s)
Dopamine , Magnetic Resonance Imaging/methods , Nanoparticles , Peptides , Phototherapy , Photothermal Therapy , Polymers
19.
Journal of Biomedical Engineering ; (6): 207-216, 2022.
Article in Chinese | WPRIM | ID: wpr-928216

ABSTRACT

With the development of photothermal nanomaterials, photothermal therapy based on near-infrared light excitation shows great potential for the bacterial infected wound treatment. At the same time, in order to improve the photothermal antibacterial effect of wound infection and reduce the damage of high temperature and heat to healthy tissue, the targeted bacteria strategy has been gradually applied in wound photothermal therapy. In this paper, several commonly used photothermal nanomaterials as well as their targeted bacterial strategies were introduced, and then their applications in photothermal antibacterial therapy, especially in bacterial infected wounds were described. Besides, the challenges of targeted photothermal antibacterial therapy in the wound healing application were analyzed, and the development of photothermal materials with targeted antibacterial property has prospected in order to provide a new idea for wound photothermal therapy.


Subject(s)
Humans , Anti-Bacterial Agents/pharmacology , Nanostructures/therapeutic use , Staphylococcus aureus , Wound Healing , Wound Infection/therapy
20.
Acta Pharmaceutica Sinica B ; (6): 2710-2730, 2022.
Article in English | WPRIM | ID: wpr-939936

ABSTRACT

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.

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