Mesoporous silica nanoparticles (MSNs) have been well‐demonstrated as excellent carriers for anticancer drug delivery. Presented here is a cancer‐targeted MSNs drug delivery system that allows the direct fluorescence monitoring of the cellular uptake and localization of theranostic agents in cancer cells. Specifically, the anticancer action mechanisms of RGD peptide‐functionalized MSNs carrying ruthenium polypyridyl complexes (RuPOP@MSNs) are elucidated in detail. RGD peptide surface decoration significantly enhances the cellular uptake of the nanoparticles through receptor‐mediated endocytosis, and increases the selectivity between cancer and normal cells. RuPOP@MSNs exhibits unprecedented enhanced cytotoxicity toward cancer cells overexpressing integrin receptor, which is significantly higher than that of free RuPOP, through induction of apoptosis. The important contribution of extrinsic pathway to cell apoptosis is confirmed by increase in expression levels of death receptors, activation of caspase‐8 and truncation of Bid. The internalized nanoparticles release free RuPOP into the cytoplasm, where they modulate the phosphorylation of p53, AKT, and MAPKs pathways to promote cell apoptosis. Moreover, the strong autofluorescence of RuPOP permits the direct monitoring of drug delivery, and extends the power of theranostics to subcellular level. Taken together, this study provides an effective strategy for the design and development of cancer‐targeted theranostic agents.
Nonspecific absorption and clearance of nanomaterials during circulation is the major cause for treatment failure in nanomedicine-based cancer therapy. Therefore, herein bioinspired red blood cell (RBC) membrane is employed to camouflage 2D MoSe 2 nanosheets with high photothermal conversion efficiency to achieve enhanced hemocompatibility and circulation time by preventing macrophage phagocytosis. RBC-MoSe 2 -potentiated photothermal therapy (PTT) demonstrates potent in vivo antitumor efficacy, which triggers the release of tumor-associated antigens to activate cytotoxic T lymphocytes and inactivate the PD-1/PD-L1 pathway to avoid immunologic escape. Furthermore, in the ablated tumor microenvironment, the tumor-associated macrophages are effectively reprogrammed to tumoricidal M1 phenotype to potentiate the antitumor action. Taken together, this biomimetic functionalization thus provides a substantial advance in personalized PTT-triggered immunotherapy for clinical translation.
Cancer
radiotherapy suffers from drawbacks such as radiation resistance
of hypoxic cells, excessive radiation that causes damage of adjacent
healthy tissues, and concomitant side effects. Hence, radiotherapy
sensitizers with improved radiotherapeutic performance and requiring
a relatively small radiation dose are highly desirable. In this study,
a nanosystem based on poly(lactic-co-glycolic acid)
(PLGA) and ultrasmall black phosphorus quantum dots (BPQDs) is designed
and prepared to accomplish precise tumor radiosensitization. The PLGA
nanoparticles act as carriers to package the BPQDs to avoid off-target
release and rapid degradation during blood circulation. The nanosystem
that targets the polypeptide peptide motif Arg-Gly-Asp-Gys actively
accumulates in tumor tissues. The 2,3-dimethylmaleic anhydride shell
decomposes in an acidic microenvironment, and the nanoparticles become
positively charged, thereby favoring cellular uptake. Furthermore,
glutathione (GSH) deoxidizes the disulfide bond of cystamine and sequentially
triggers release of BPQDs, rendering tumor cells sensitive to radiotherapy.
The treatment utilizing the PLGA‑SS‑D@BPQDs
nanosystem and X-ray induces cell apoptosis triggered by overproduction
of reactive oxygen species. In the in vivo study,
the nanosystem shows excellent radiotherapy sensitization efficiency
but negligible histological damage of the major organs. This study
provides insights into the design and fabrication of surface-charge-switching
and pH-responsive nanosystems as potent radiosensitizers to achieve
excellent radiotherapy sensitization efficacy and negligible toxic
side effects.
Radiotherapy displays curative potential for cervical cancer management, but radioresistance occurs during long-term therapy. To overcome this limitation, tumor-targeted nanotechnology has been proposed to enhance the radiosensitivity of solid tumors. Herein, we used biocompatible bovine serum albumin nanoparticles (BSANPs) as carriers of organic selenocompound (PSeD) with folate (FA) as the targeting ligand to fabricate a cancer-targeted nanosystem. The combination of PSeD and BSANPs endowed the nanosystem with higher light absorption and reactive oxygen species (ROS) generation owing to their properties of surface plasmon resonance (SPR) effect, heavy metal effect, high refractive index and nanoparticulate interfacial effect. The combined treatment drastically increased the ROS overproduction, VEGF/VEGFR2 inactivation and inhibition of XRCC-1-mediated repair of DNA damage, thus triggering G2/M phase arrest and apoptosis. Taken together, our findings demonstrate the utility of FA-BSANPs as a promising radiosensitizer to improve cancer radiotherapy.
The chirality of nanoparticles directly influences their transport and biological effects under physiological conditions, but the details of this phenomenon have rarely been explored. Herein, chiral GSH‐anchored selenium nanoparticles (G@SeNPs) are fabricated to investigate the effect of their chirality on their transport and antioxidant activity. G@SeNPs modified with different enantiomers show opposite handedness with a tunable circular dichroism signal. Noninvasive positron emission tomography imaging clearly reveals that 64Cu‐labeled l‐G@SeNPs experience distinctly different transport among the major organs from that of their d‐and dl‐counterparts, demonstrating that the chirality of the G@SeNPs influences the biodistribution and kinetics. Taking advantage of the strong homologous cell adhesion and uptake, l‐G@SeNPs have been shown here to effectively prevent oxidation damage caused by palmitic acid in insulinoma cells.
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