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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)].
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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 useABSTRACT
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/chemistryABSTRACT
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.
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Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide, and hepatocellular carcinoma is the main type of primary liver cancer. HCC is insidious and asymptomatic at an early stage, and when clinically relevant, the disease is often in the middle to late stages. As a result, most patients miss out on radical treatment at the time of diagnosis, leading to high recurrence and metastasis rates and poor prognosis. At present, there are more and more methods in the treatment of hepatocellular carcinoma. Photothermal therapy, as an emerging cancer treatment, has attracted widespread attention due to its minimally invasive, low-cost, high efficiency, low side effects and strong targeting. Research progress of photothermal therapy and its synergistic therapy in the treatment of hepatocellular carcinoma were reviewed in this paper, aiming to explore new ideas and strategies for the treatment of hepatocellular carcinoma.
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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.
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Objective:To prepare a phase-change lipid nanoparticle modified by tumor homing membrane-penetrating peptide (tLyP-1) and carrying paclitaxel (PTX) engineered by metal polyphenol network (TA-Fe 3+ ), and evaluate the therapeutic effects of tumor targeting, ultrasound/photoacoustic imaging and photothermal combined chemotherapy in vitro. Methods:Phase-change lipid nanoparticles (t-P@TFP) with TA-Fe 3+ engineered PTX mediated by tLyP-1 were prepared by solvent replacement method, thin film hydration method and double emulsification method. Its detection and characterization, in vitro targeting ability, photothermal conversion ability, in vitro photoacoustic and ultrasonic imaging ability, CCK-8 method, cell live and death double staining method and flow cytometry method were used to detect the safety of nanoparticles and the killing effects of different nanoparticles on 4T1 cells. Results:t-P@TFP nanoparticles were successfully prepared. Transmission electron microscopy showed that the nanoparticles were spherical with uniform shape and size, with a particle size of (209.8±1.56)nm and a potential of (-25.9±1.36)mV. Laser confocal scanning microscopy showed that t-P@TFP nanoparticles could gather around 4T1 cells in a targeted manner. It had an efficient photothermal conversion effect, and nanoparticles could quickly become microbubbles after being irradiated by near-infrared laser, which enhanced the in vitro ultrasonic imaging effect; The photoacoustic signal of nanoparticles increased with the increase of concentration. CCK-8 method, double staining of living and dead cells and flow cytometry showed that t-P@TFP combined photothermal chemotherapy had the best anti-tumor effect. Conclusions:t-P@TFP nanoparticles are successfully prepared. The nanoparticles have good targeting ability for photoacoustic and ultrasonic imaging and have good photothermal effect, killing breast cancer cells, which is expected to realize the integration of diagnosis and treatment.
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Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
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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.
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Objective To explore whether inhibiting autophagy can enhance the sensitivity of photothermal treatment under mild photothermal conditions. Methods CQ@PLGA@PDA NPs were prepared by an improved double emulsification method and a PDA-based surface modification method. After basic characterization, CCK-8 method was used to detect the cytotoxicity of nanoparticles; the near-infrared laser irradiation nanoparticle solution was used to detect the heating effect; CCK-8 method and live-dead cell staining were used to detect the killing effect of tumor cells; Western blot was used to detect the expression of autophagy-related proteins. Results The CQ@PLGA@PDA NPs were successfully prepared, with a particle size of 253.10±2.39 nm, a zeta potential of -22.57±0.80 mV, uniform particle size and good dispersion. The temperature of nanoparticle solution increased to 45℃ after the near-infrared laser irradiation for 10 min. CQ@PLGA@PDA NPs had no obvious toxicity to cells. The survival rates of breast cancer cell MDA-MB-231 and mouse embryonic fibroblast NIH-3T3 cell were above 95%. The inhibition of autophagy under mild photothermal conditions could improve the sensitivity of photothermal therapy. Conclusion The prepared CQ@PLGA@PDA NPs have good photothermal performance and high biological safety; by inhibiting autophagy, they can effectively kill tumor cells under mild photothermal conditions(< 50℃).
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In recent years, the research on gold nanoparticles has made great progress. Gold nanoparticles with different morphologies have good application prospects in drug delivery and tumor treatment. Some gold nanoparticles have entered the stage of clinical trials. Gold nanorods have become important research objects due to their special optical properties and photothermal treatment potential. In this paper, the optical properties and main applications of gold nanorods were reviewed. Gold nanorods have good surface modifiable properties and can be modified through surface ligand exchange to improve their biocompatibility. The photothermal properties of gold nanorods can be improved by adjusting the aspect ratio to adjust the surface plasmon resonance (SPR) peak to achieve near-infrared light excitation. These characteristics make gold nanorods show good application prospects in the detection of biological macromolecules, real-time imaging in vivo, and early diagnosis and treatment of tumors. Using gold nanorods as a carrier and modified with different targeting molecules can improve the targeting of its drug delivery system and reduce damage to normal cells, so as to realize the combined application of chemotherapy and photothermal therapy, and finally achieve a better therapeutic effect. Combining gold nanorods with stem cells or certain specific biomolecules can form a hybrid gold nanorod system which provides new ideas for further improving the efficiency of tumor treatment.
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@#To improve the therapeutic effect of cisplatin and reduce its side effects, a multifunctional drug delivery system with targeted and chemo-photothermal effect was constructed.Using polyethylene glycol polylactic acid block copolymer as a carrier, nanoparticles loaded with antitumor drug cisplatin and photosensitizer indocyanine green were prepared by ultrasonic emulsification, and the surface was then modified by cetuximab to prepare cetuximab-decorated and near-infrared (NIR)-activated nanoparticles (CPINPs).The physicochemical properties were characterized by mean particle size, Zeta potential, mAb conjugating rate and photothermal effect; the in vitro cell uptake was measured by laser confocal microscopy; and the in vitro antitumor activity was evaluated by CCK8 assay.The results indicated that CPINPs had mean particle diameter of (263.9 ± 3.73) nm, polydispersity index of 0.18 ± 0.03, Zeta potential of -(23.43 ± 0.42) mV, and cetuximab conjugating rate of (44.0 ± 1.72)%.The in vitro photothermal experiments showed that CPINPs upon NIR irradiation induced a photothermal effect, thus destroying the tumor cells. The in vitro cell uptake experiments demonstrated that NIR irradiation could promote cell uptake, and that more CPINPs were effectively internalized into A549 cells. The in vitro cytotoxicity test indicated that CPINPs treated with NIR irradiation had the effect of combined chemo-photothermal therapy, leading to higher cytotoxicity than that of free cisplatin or treatment without NIR, with IC50 values being (8.67 ± 0.04) μmol/L for 24 h incubation.To sumup the multifunctional drug delivery system constructed in the current work expected to be a more efficient targeted therapy strategy for lung cancer.
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The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer. In present study, nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2 (MMP-2) dual-responsive, tumor targeting, and size-variability were designed for enhancing the antitumor efficacy and achieving "on-demand" drug release markedly. Based on the thermal sensitivity of gelatin, we designed a size-variable gelatin nanoparticle (GNP) to encapsulate indocyanine green (ICG) and doxorubicin (DOX). Under an 808 nm laser irradiation, GNP-DOX/ICG responded photothermally and swelled in size from 71.58 ± 4.28 to 160.80 ± 9.51 nm, which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics. Additionally, GNP-DOX/ICG showed a size reduction of the particles to 33.24 ± 4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor. In the subsequently performed