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1.
Article in English | MEDLINE | ID: mdl-39004508

ABSTRACT

Nanomedicines have significantly advanced the development of diagnostic and therapeutic strategies for various diseases, while they still encounter numerous challenges. Upon entry into the human body, nanomedicines interact with biomolecules to form a layer of proteins, which is defined as the protein corona that influences the biological properties of nanomedicines. Traditional approaches have primarily focused on designing stealthy nanomedicines to evade biomolecule adsorption; however, due to the intricacies of the biological environment within body, this method cannot completely prevent biomolecule adsorption. As research on the protein corona progresses, manipulating the protein corona to modulate the in vivo behaviors of nanomedicines has become a research focus. In this review, modern strategies focused on influencing the biological efficacy of nanomedicines in vivo by manipulating protein corona, along with their wide-ranging applications across diverse diseases are critically summarized, highlighted and discussed. Finally, future directions for this important yet challenging research area are also briefly discussed. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.


Subject(s)
Nanomedicine , Protein Corona , Protein Corona/chemistry , Humans , Animals , Drug Delivery Systems
2.
Biomater Sci ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007343

ABSTRACT

Although the current surgical hematoma removal treatment saves patients' lives in critical moments of intracerebral hemorrhage (ICH), the lethality and disability rates of ICH are still very high. Due to the individual differences of patients, postoperative functional improvement is still to be confirmed, and the existing drug treatment has limited benefits for ICH. Recent advances in biomaterials may provide new ideas for the therapy of ICH. This review first briefly describes the pathogenic mechanisms of ICH, including primary and secondary injuries such as inflammation and intracerebral edema, and briefly describes the existing therapeutic approaches and their limitations. Secondly, existing nanomaterials and hydrogels for ICH, including exosomes, liposomes, and polymer nanomaterials, are also described. In addition, the potential challenges and application prospects of these biomaterials for clinical translation in ICH treatment are discussed.

3.
Acta Pharm Sin B ; 14(4): 1787-1800, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38572091

ABSTRACT

Radiotherapy (RT) is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors. In particular, immune responses triggered by RT, known as radio-immunotherapy, can partially inhibit the growth of distantly spreading tumors and recurrent tumors. However, the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immunogenicity of tumor. Herein, we report oxaliplatin (IV)-iron bimetallic nanoparticles (OXA/Fe NPs) as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy. The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA (II) and Fe2+ in response to the reductive and acidic microenvironment within tumor cells. The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage, increasing ROS and O2 levels, and amplifying the immunogenic cell death (ICD) effect after RT to facilitate potent immune activation. As a result, OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect. Moreover, a long-term immunological memory effect to protect mice from tumor rechallenging is observed. Overall, the bimetallic NPs-based cascade sensitizing amplifier system offers an efficient radio-immunotherapy regimen that addresses the key challenges.

4.
Adv Sci (Weinh) ; 11(13): e2307798, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38279574

ABSTRACT

Developing nanozymes with effective reactive oxygen species (ROS) scavenging ability is a promising approach for osteoarthritis (OA) treatment. Nonetheless, numerous nanozymes lie in their relatively low antioxidant activity. In certain circumstances, some of these nanozymes may even instigate ROS production to cause side effects. To address these challenges, a copper-based metal-organic framework (Cu MOF) nanozyme is designed and applied for OA treatment. Cu MOF exhibits comprehensive and powerful activities (i.e., SOD-like, CAT-like, and •OH scavenging activities) while negligible pro-oxidant activities (POD- and OXD-like activities). Collectively, Cu MOF nanozyme is more effective at scavenging various types of ROS than other Cu-based antioxidants, such as commercial CuO and Cu single-atom nanozyme. Density functional theory calculations also confirm the origin of its outstanding enzyme-like activities. In vitro and in vivo results demonstrate that Cu MOF nanozyme exhibits an excellent ability to decrease intracellular ROS levels and relieve hypoxic microenvironment of synovial macrophages. As a result, Cu MOF nanozyme can modulate the polarization of macrophages from pro-inflammatory M1 to anti-inflammatory M2 subtype, and inhibit the degradation of cartilage matrix for efficient OA treatment. The excellent biocompatibility and protective properties of Cu MOF nanozyme make it a valuable asset in treating ROS-related ailments beyond OA.


Subject(s)
Metal-Organic Frameworks , Osteoarthritis , Humans , Antioxidants/pharmacology , Copper , Reactive Oxygen Species , Osteoarthritis/drug therapy
5.
Nat Commun ; 15(1): 107, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38167880

ABSTRACT

Bacteria-associated infections and thrombosis, particularly catheter-related bloodstream infections and catheter-related thrombosis, are life-threatening complications. Herein, we utilize a concise assembly of heparin sodium with organosilicon quaternary ammonium surfactant to fabricate a multifunctional coating complex. In contrast to conventional one-time coatings, the complex attaches to medical devices with arbitrary shapes and compositions through a facile dipping process and further forms robust coatings to treat catheter-related bloodstream infections and thrombosis simultaneously. Through their robustness and adaptively dissociation, coatings not only exhibit good stability under extreme conditions but also significantly reduce thrombus adhesion by 60%, and shows broad-spectrum antibacterial activity ( > 97%) in vitro and in vivo. Furthermore, an ex vivo rabbit model verifies that the coated catheter has the potential to prevent catheter-related bacteremia during implantation. This substrate-independent and portable long-lasting multifunctional coating can be employed to meet the increasing clinical demands for combating catheter-related bloodstream infections and thrombosis.


Subject(s)
Bacteremia , Bacterial Infections , Thrombosis , Animals , Rabbits , Heparin/pharmacology , Catheters/microbiology , Anti-Bacterial Agents/pharmacology , Thrombosis/drug therapy , Thrombosis/prevention & control
6.
Macromol Biosci ; 24(2): e2300116, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37677756

ABSTRACT

The effectiveness of chemotherapy is primarily hindered by drug resistance, and autophagy plays a crucial role in overcoming this resistance. In this project, a human transferrin nanomedicine contains quercetin (a drug to induce excessive autophagy) and doxorubicin is developed (HTf@DOX/Qu NPs). The purpose of this nanomedicine is to enhance mitophagy and combating drug-resistant cancer. Through in vitro studies, it is demonstrated that HTf@DOX/Qu NPs can effectively downregulate cyclooxygenase-2 (COX-2), leading to an excessive promotion of mitophagy and subsequent mitochondrial dysfunction via the PENT-induced putative kinase 1 (PINK1)/Parkin axis. Additionally, HTf@DOX/Qu NPs can upregulate proapoptotic proteins to induce cellular apoptosis, thereby effectively reversing drug resistance. Furthermore, in vivo results have shown that HTf@DOX/Qu NPs exhibit prolonged circulation in the bloodstream, enhanced drug accumulation in tumors, and superior therapeutic efficacy compared to individual chemotherapy in a drug-resistant tumor model. This study presents a promising strategy for combating multidrug-resistant cancers by exacerbating mitophagy through the use of transferrin nanoparticles.


Subject(s)
Nanoparticles , Neoplasms , Humans , Nanomedicine/methods , Mitophagy , Transferrin , Doxorubicin/pharmacology
7.
Opt Express ; 31(22): 35632-35643, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-38017730

ABSTRACT

The generation of multi-mode vortex beams at the same aperture is currently emerging as a research hotspot. In this paper, a method based on a linearly polarized-circularly polarized translational transmission metasurface (TM) is proposed to enable a dual-circularly polarized dual-mode vortex beam generation. Through the judicious implementation of an additional rotational phase and the combination of the initial transmission phase, the phases of the left-hand circularly polarized (LHCP) and right-hand circularly polarized (RHCP) waves can be manipulated arbitrarily and independently. Meanwhile, the design of the array phase is utilized for the dual-mode dual-circularly polarized beam generation. Simulation and sample measurements provide validation data for the feasibility of this method, in which the measurement results are in excellent consistency with the simulation ones. This proposed method paves the way toward the enhancement of the channel capacity of mobile communication.

8.
J Nanobiotechnology ; 21(1): 215, 2023 Jul 08.
Article in English | MEDLINE | ID: mdl-37422665

ABSTRACT

It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.


Subject(s)
COVID-19 , Metal Nanoparticles , Nanoparticles , Pulmonary Fibrosis , Humans , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Gold/metabolism , Administration, Inhalation , COVID-19/metabolism , Drug Delivery Systems , Lung/metabolism , Pharmaceutical Preparations/metabolism , Nanoparticles/therapeutic use
9.
ACS Appl Mater Interfaces ; 15(33): 39064-39080, 2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37523857

ABSTRACT

No current pharmacological approach is capable of simultaneously inhibiting the symptomatology and structural progression of osteoarthritis. M1 macrophages and activated synovial fibroblasts (SFs) mutually contribute to the propagation of joint pain and cartilage destruction in osteoarthritis. Here, we report the engineering of an apoptotic neutrophil membrane-camouflaged liposome (termed "NM@Lip") for precise delivery of triamcinolone acetonide (TA) by dually targeting M1 macrophages and activated SFs in osteoarthritic joints. NM@Lip has a high cellular uptake in M1 macrophages and activated SFs. Furthermore, TA-loaded NM@Lip (TA-NM@Lip) effectively repolarizes M1 macrophages to the M2 phenotype and transforms pathological SFs to the deactivated phenotype by inhibiting the PI3K/Akt pathway. NM@Lip retains in the joint for up to 28 days and selectively distributes into M1 macrophages and activated SFs in synovium with low distribution in cartilage. TA-NM@Lip decreases the levels of pro-inflammatory cytokines, chemokines, and cartilage-degrading enzymes in osteoarthritic joints. In a rodent model of osteoarthritis-related pain, a single intra-articular TA-NM@Lip injection attenuates synovitis effectively and achieves complete pain relief with long-lasting effects. In a rodent model of osteoarthritis-related joint degeneration, repeated intra-articular TA-NM@Lip injections induce no obvious cartilage damage and effectively attenuate cartilage degeneration. Taken together, TA-NM@Lip represents a promising nanotherapeutic approach for osteoarthritis therapy.


Subject(s)
Liposomes , Osteoarthritis , Humans , Liposomes/metabolism , Neutrophils/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Osteoarthritis/pathology , Macrophages , Fibroblasts/metabolism , Pain/metabolism
10.
J Control Release ; 356: 567-579, 2023 04.
Article in English | MEDLINE | ID: mdl-36924894

ABSTRACT

Polyprodrug nanomedicines hold great potential for combating tumors. However, the functionalization of polyprodrug nanomedicines to improve therapeutic efficacy is restricted by conventional polymerization methods. Herein, we fabricated a charge-conversional click polyprodrug nanomedicine system by metal-free azide-alkyne cycloaddition click polymerization (AACCP) for targeted and synergistic cancer therapy. Specifically, Pt(IV) prodrug-backboned diazide monomer, DMC prodrug-pendent diazide monomer, dialkyne-terminated PEG monomer and azide-modified folate were click polymerized to obtain the target polyprodrug (P1). P1 could self-assemble into nano-micelles (1-NM), where PEG was the hydrophilic shell with folate on the surface, Pt(IV) and DMC prodrugs as the hydrophobic core. Taking advantage of PEGylation and folate-mediated tumor cell targeting, 1-NM achieved prolonged blood circulation time and high tumor accumulation efficiency. Tumor acidic microenvironment-responsive cleavage and cascade activation of pendant DMC prodrug induced surface charge conversion of 1-NM from negative to positive, which promoted tumor penetration and cellular internalization of the remaining 1-NM. After internalization into tumor cells, the reduction-responsive activation of Pt(IV) prodrug to Pt(II) further showed synergetic effect with DMC for enhanced apoptosis. This first designed charge-conversional click polyprodrug nanomedicine exhibited targeted and synergistic efficacy to suppress tumor proliferation in living mice bearing human ovarian tumor model.


Subject(s)
Neoplasms , Prodrugs , Mice , Humans , Animals , Prodrugs/chemistry , Nanomedicine , Azides , Neoplasms/metabolism , Micelles , Cell Line, Tumor , Tumor Microenvironment
11.
J Mater Chem B ; 11(8): 1808-1817, 2023 02 22.
Article in English | MEDLINE | ID: mdl-36734460

ABSTRACT

Photodynamic therapy (PDT) has attracted much attention in recent years for its favorable therapeutic efficacy in cancer therapy. However, PDT alone is insufficient to improve the therapeutic efficiency mainly due to the limited penetration depth of light, the insufficient O2 supply in the hypoxic microenvironment, and the high level of reducing substances in cancer cells. To overcome these limitations, a multifunctional MnO2 nanoparticle was constructed with honeycomb MnO2 which was loaded with the photosensitizer Ce6 and modified with polydopamine on its surface (HMnO2/C&P) to achieve efficient PDT/mild photothermal treatment (PTT) combination therapy. HMnO2/C&P had high drug loading contents (11.2% Ce6) and can be responsive to the tumor microenvironment (TME), supply O2 to alleviate the hypoxic microenvironment, and clear GSH to reduce the consumption of ROS, thus enhancing the PDT effect. The introduction of PDA can improve the stability of HMnO2/C&P, and further give the ability of PTT to act as nanomedicine. The results of in vitro and in vivo experiments show that HMnO2/C&P based PDT/mild PTT combination therapy has an excellent inhibitory effect on tumor growth. Meanwhile, HMnO2/C&P can act as a fluorescence imaging reagent and a TME triggerable magnetic resonance imaging (MRI) contrast agent, thus having excellent multimodal self-tracking abilities. Collectively, this study provides a new perspective on the design of multifunctional theranostic nanomedicine to maximize the efficacy of cancer phototherapy.


Subject(s)
Photochemotherapy , Theranostic Nanomedicine , Theranostic Nanomedicine/methods , Manganese Compounds , Oxides , Phototherapy , Photochemotherapy/methods , Contrast Media
12.
Microorganisms ; 11(2)2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36838341

ABSTRACT

Controlled environment agriculture hydroponic systems grow plants year-round without restriction from outside environmental conditions. In order to further improve crop yield, plant growth-promoting bacteria were tested on hydroponically grown lettuce (Lactuca sativa) plants. From our bacterial endophyte library, we found one bacterium, Pseudomonas psychrotolerans IALR632, that is promising in promoting lettuce growth in multiple hydroponic systems. When Green Oakleaf lettuce seeds were inoculated with IALR632 during germination, IALR632 significantly increased lateral root development by 164%. When germinated seedlings were inoculated with IALR632 and then transplanted to different hydroponic systems, shoot and root fresh weights of Green Oakleaf increased by 55.3% and 17.2% in a nutrient film technique (NFT) system in the greenhouse, 13.5% and 13.8% in an indoor vertical NFT system, and 15.3% and 13.6% in a deep water cultivation (DWC) system, respectively. IALR632 also significantly increased shoot fresh weights of Rex by 33.9%, Red Oakleaf by 21.0%, Red Sweet Crisp by 15.2%, and Nancy by 29.9%, as well as Red Rosie by 8.6% (no significant difference). Inoculation of IALR632-GFP and subsequent analysis by confocal microscopy demonstrated the endophytic nature and translocation from roots to shoots. The results indicate that P. psychrotolerans IALR632 has a potential application in hydroponically grown lettuce plants.

13.
Biomaterials ; 289: 121793, 2022 10.
Article in English | MEDLINE | ID: mdl-36126545

ABSTRACT

Chemoradiotherapy is a widely used treatment for patients with malignancies such as hepatocellular carcinoma (HCC). However, it remains challenging to realize safe and synergistic chemotherapy and radiation sensitization. Herein, we design a self-targeting nano-assembly (STNA) based on platinum(IV)-lactose amphiphilic prodrug for synergistic and safe chemoradiotherapy of HCC. The Pt STNA would improve the tumor accumulation due to the targeting ability of lactose to HCC cells. After receptor-mediated endocytosis, Pt STNA would release cisplatin(II) in cancer cells to form DNA-binding, thus inducing DNA damage and cell apoptosis. Meanwhile, the DNA-binding also causes cell cycle arrest in the radiation-sensitive G2/M phase by the up-regulation of phosphorylated checkpoint kinase 1 (p-Chk1) expression. Furthermore, under X-ray irradiation, Pt STNA as radiosensitizer possesses a strong X-ray attenuation ability to deposit more energy, thus elevating the level of reactive oxygen species (ROS) to amplify the cell-killing effect of radiotherapy in the G2/M phase with increased DNA damage. As a result, Pt STNA exhibits significant synergistic therapeutic effects in chemoradiotherapy with no adverse effects in vitro and in vivo. Overall, we present a novel self-targeting nano-assembly strategy based on widely used Pt drugs for synergistic chemotherapy and radiation sensitization of HCC treatment.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Prodrugs , Radiation-Sensitizing Agents , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Checkpoint Kinase 1 , Chemoradiotherapy , Cisplatin/therapeutic use , DNA/therapeutic use , Humans , Lactose/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Platinum/therapeutic use , Prodrugs/pharmacology , Radiation-Sensitizing Agents/pharmacology , Radiation-Sensitizing Agents/therapeutic use , Reactive Oxygen Species/metabolism
14.
Int J Biol Macromol ; 221: 923-933, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36089087

ABSTRACT

Cartilage defect is one of the most common pathogenesis of osteoarthritis (OA), a degenerative joint disease that affects millions of people globally. Due to lack of nutrition and local metabolic inertia, the repair of cartilage has always been a difficult problem to be urgently solved. Herein, a functional gelatin hydrogel scaffold (GelMA-AG) chemically modified with alanyl-glutamine (AG) is proposed and prepared. The GelMA-AG can release glutamine through in vivo degradation that can activate the energy metabolism process of chondrocytes, thus effectively promoting damaged cartilage repair. The results demonstrate that compared with the AG-free gelatin hydrogel (GelMA), GelMA-AG exhibits an increase in both the mitochondrial membrane potential level and the production of intracellular adenosine triphosphate (ATP), while the intracellular reactive oxygen species (ROS) of chondrocytes is decreased, thus contributing to the higher level of cellular metabolism and the lower inflammation in cartilage tissue. In contrast to GelMA (Reduced Modulus (Er): 24.33 MPa), the Er value of the remodeled rabbit knee articular cartilage is up to 70.14 MPa, which is more comparable to natural cartilage. In particular, this strategy does not involve exogenous cells and growth factors, and the therapeutic strategy of actively regulating the metabolic microenvironment through a functional gelatin hydrogel scaffold represents a new and prospective idea for the design of tissue engineering biomaterials in cartilage repair with simplification and effectiveness.


Subject(s)
Cartilage, Articular , Gelatin , Animals , Rabbits , Hydrogels/pharmacology , Glutamine , Prospective Studies , Tissue Engineering/methods , Energy Metabolism , Tissue Scaffolds
15.
ACS Omega ; 7(33): 29256-29265, 2022 Aug 23.
Article in English | MEDLINE | ID: mdl-36033651

ABSTRACT

Current cancer treatment is not only limited to monotherapy but is also influenced by limited drug delivery options. Combined chemokinetic-photokinetic therapy has great promise in enhancing anticancer effects. Meanwhile, zein has superior self-assembly properties and can be loaded with photosensitizers. Herein, the targeted multifunctional nanoparticles based on zein/hyaluronate acid (HA)/tannin (TA)/Cu2+ loaded with IR780 (ZHTC@IR780) are constructed for synergetic cancer therapy by chemo-dynamic therapy (CDT) and photodynamic therapy (PDT). There is experimental proof that ZHTC@IR780 nanoparticles (NPs) can relieve the tumor hypoxic microenvironment by catalytic decomposition of endogenous H2O2 to O2 and further react with O2 to produce toxic 1O2 with 808 nm laser irradiation. The glutathione oxidase-like effects of ZHTC@IR780 NPs can generate Fenton-like Cu+ ions and deplete GSH for efficient hydroxyl radical (•OH) production. In addition, CDT combined with PDT enhances the antitumor effect. Photodynamic therapy can cause immunogenic cell death, increase calreticulin eversion, release histone with high mobility, and promote apoptosis of tumor cells.

16.
Sensors (Basel) ; 22(12)2022 Jun 09.
Article in English | MEDLINE | ID: mdl-35746143

ABSTRACT

To improve the accuracy of the current vision-based linear displacement measurement in a large range, a new type of linear displacement sensing system, namely, image grating, is proposed in this paper. The proposed system included a patterned glass plate attached to the moving object and an ultra-low distortion lens for high-accuracy image matching. A DFT local up-sampling phase correlation method was adopted to obtain the sub-pixel translation of the patterns onto the target plate. Multiple sets of stripe patterns with different designs were located on the glass plate to expand the measurement range, based on the principle of phase correlation. In order to improve the measurement accuracy, the main errors of the image grating system were analyzed, and the nonlinear error compensation was completed based on the dynamic calibration of the pixel equivalent. The measurement results, after the error compensation, showed that the total error of the proposed system was less than 2.5 µm in the range of 60 mm, and the repeatability was within 0.16 µm, as quantified by standard deviation.

17.
ACS Biomater Sci Eng ; 8(6): 2526-2536, 2022 06 13.
Article in English | MEDLINE | ID: mdl-35612599

ABSTRACT

Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.


Subject(s)
Antineoplastic Agents , Ovarian Neoplasms , Prodrugs , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cisplatin/pharmacology , Cisplatin/therapeutic use , Female , Humans , Lactones , Ovarian Neoplasms/drug therapy , Platinum/pharmacology , Platinum/therapeutic use , Polyethylene Glycols/therapeutic use , Prodrugs/pharmacology , Prodrugs/therapeutic use , Sesquiterpenes, Eudesmane
18.
Nano Lett ; 22(11): 4410-4420, 2022 06 08.
Article in English | MEDLINE | ID: mdl-35575719

ABSTRACT

Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancers, but achieving multitarget therapy of TAMs is still challenging. Here, we develop a protein-crowned micelle system for targeted and synergistic TAM reprogramming to enhance cancer treatment. The doxorubicin-loaded micelles with a hemoglobin crown (Hb-DOXM) can bind with endogenous plasma haptoglobin to realize specific M2-type TAM targeting. Under the tumor hypoxic and acidic environments, Hb-DOXM can responsively release O2 and DOX to reduce the recruitment of TAMs by hypoxia remission and release DOX to kill M2-type TAMs and cancer cells. To reprogram TAMs adequately, the TAM-modulating drug celecoxib is further encapsulated (Hb-DOXM@Cel) to repolarize M2-type TAMs. The targeted and synergistic TAM reprogramming by Hb-DOXM@Cel can remodel the tumor microenvironment (TME) to an immunostimulatory microenvironment and augment the antitumor effect of cytotoxic T lymphocyte, thus strongly enhancing the DOX-based chemotherapy. The protein-crowned micelle strategy presents a targeted and synergistic TAM therapy tool for enhanced cancer treatment.


Subject(s)
Neoplasms , Tumor-Associated Macrophages , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Humans , Immunotherapy , Micelles , Neoplasms/drug therapy , Tumor Microenvironment
19.
Small ; 18(20): e2200993, 2022 05.
Article in English | MEDLINE | ID: mdl-35451111

ABSTRACT

Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV. The nano-adjuvant displays a deep tumor penetration capacity via loosening the dense extracellular matrix of tumors. Upon NIR-II light irradiation, the nano-adjuvant significantly inhibits the tumor growth, induces a cascade of immune responses, generates an obvious adaptive immunity against the re-challenged cancers, boosts the abscopal effect, and completely inhibits the pulmonary metastases. The study highlights an advanced nano-adjuvant formulation featuring deep tumor penetration for NIR-II-triggered ISTV.


Subject(s)
Gold , Neoplasms , Cell Line, Tumor , Humans , Infrared Rays , Neoplasms/therapy , Phototherapy , Vaccination
20.
ACS Nano ; 16(4): 6835-6846, 2022 04 26.
Article in English | MEDLINE | ID: mdl-35412302

ABSTRACT

Theranostics of platinum (Pt)-based chemotherapy are able to self-track the biodistribution and pharmacokinetics while performing therapeutic effects. Pt-based CT imaging is expected to visualize and monitor the tumor throughout the entire tumor inhibition stage. However, a sufficient Pt concentration is necessary for CT imaging, which may bring about severe nephrotoxicity. A Bio-Pt-I compound is designed and synthesized by conjugation of iodine and biotin to the structure of Pt and further self-assembles into nanoparticles. The introduction of iodine not only enhances the CT imaging signal with a much lower dose of Pt but also overcomes the resistance of tumor cells to Pt-containing nanomedicine by inhibiting the expression of Bcl-2. Furthermore, biotin-mediated tumor targeting increases drug accumulation in tumors. This work combines CT imaging based self-track with efficient cisplatin-resistance reversion ability, which may promote the clinical transformation of Pt-containing nanomedicine.


Subject(s)
Antineoplastic Agents , Iodine , Nanoparticles , Neoplasms , Humans , Platinum/chemistry , Theranostic Nanomedicine/methods , Biotin , Iodine/therapeutic use , Tissue Distribution , Antineoplastic Agents/chemistry , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/metabolism , Cisplatin/pharmacology , Cisplatin/therapeutic use , Tomography, X-Ray Computed , Cell Line, Tumor
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