Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, a narrow therapeutic window, and unfavorable pharmacokinetic properties. To solve the above problems, target drug delivery to tumor cells, and reduce the side effects of drugs, an anti-tumor drug delivery system based on tumor microenvironment has become a focus of research in recent years. The construction of a reduction-sensitive nanomedicine delivery system based on disulfide bonds has attracted much attention. Disulfide bonds have good reductive responsiveness and can effectively target the high glutathione (GSH) levels in the tumor environment, enabling precise drug delivery. To further enhance targeting and accelerate drug release, disulfide bonds are often combined with pH-responsive nanocarriers and highly expressed ligands in tumor cells to construct drug delivery systems. Disulfide bonds can connect drug molecules and polymer molecules in the drug delivery system, as well as between different drug molecules and carrier molecules. This article summarized the drug delivery systems (DDS) that researchers have constructed in recent years based on disulfide bond drug delivery systems targeting the tumor microenvironment, disulfide bond cleavage-triggering conditions, various drug loading strategies, and carrier design. In this review, we also discuss the controlled release mechanisms and effects of these DDS and further discuss the clinical applicability of delivery systems based on disulfide bonds and the challenges faced in clinical translation.
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA–DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA–DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA–DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
Purpose: Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors. Methods: We developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice. Results: Synthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors. Conclusion: PDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.
Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are great obstacles for drug delivery. As an important part of cell information transmission and behavior regulation, cell membrane can be used as drug coating material which represents a promising strategy and can overcome these limitations. Mesenchymal stem cell (MSC) membrane, as a new carrier, has the characteristics of active targeting and immune escape of MSC, and has broad application potential in tumor treatment, inflammatory disease, tissue regeneration and other fields. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for therapy and drug delivery, aiming to provide guidance for the design and clinical application of membrane carrier in the future.
20 September 2022 in Biomedicine & Pharmacotherapy
Prostate cancer (PCa) is the most common new cancer case and the second most fatal malignancy in men. Surgery, endocrine therapy, radiotherapy and chemotherapy are the main clinical treatment options for PCa. However, most prostate cancers can develop into castration-resistant prostate cancer (CRPC), and due to the invasiveness of prostate cancer cells, they become resistant to different treatments and activate tumor-promoting signaling pathways, thereby inducing chemoresistance, radioresistance, ADT resistance, and immune resistance. Nanotechnology, which can combine treatment with diagnostic imaging tools, is emerging as a promising treatment modality in prostate cancer therapy. Nanoparticles can not only promote their accumulation at the pathological site through passive targeting techniques for enhanced permeability and retention (EPR), but also provide additional advantages for active targeting using different ligands. This property results in a reduced drug dose to achieve the desired effect, a longer duration of action within the tumor and fewer side effects on healthy tissues. In addition, nanotechnology can create good synergy with radiotherapy, chemotherapy, thermotherapy, photodynamic therapy and gene therapy to enhance their therapeutic effects with greater scope, and reduce the resistance of prostate cancer. In this article, we intend to review and discuss the latest technologies regarding the use of nanomaterials as therapeutic and diagnostic tools for prostate cancer.