The consolidation of nanovectors with biological membranes has recently been a subject of interest owing to the prolonged systemic circulation time and delayed clearance by the reticuloendothelial system of such systems. Among the different biomembranes, the macrophage membrane has a similar systemic circulation time, with an additional chemotactic aptitude, targeting integrin proteins. In this study, we aimed to establish a laseractivated, disintegrable, and deeply tumor-penetrative nanoplatform. We used a highly tumor-ablative and laser-responsive disintegrable copper sulfide nanoparticle, loaded it with paclitaxel, and camouflaged it with the macrophage membrane for the fabrication of PTX@CuS@MMNPs. The in vitro paclitaxel release profile was favorable for release in the tumor microenvironment, and the release was accelerated after laser exposure. Cellular internalization was improved by membrane encapsulation. Cellular uptake, cytotoxicity, reactive oxygen species generation, and apoptosis induction of PTX@CuS@MMNPs were further improved upon laser exposure, and boosted permeation was achieved by co-administration of the tumor-penetrating peptide iRGD. In vivo tumor accumulation, tumor inhibition rate, and apoptotic marker expression induced by PTX@CuS@MMNPs were significantly improved by laser irradiation and iRGD co-administration. PTX@CuS@MMNPs induced downregulation of cellular proliferation and angiogenic markers but no significant changes in body weight, survival, or significant toxicities in vital organs after laser exposure, suggesting their biocompatibility. The disintegrability of the nanosystem, accredited to biodegradability, favored efficient elimination from the body. In conclusion, PTX@CuS@MMNPs showed promising traits in combination therapies for excellent tumor eradication.
Cell-based
delivery platforms have received great interest in recent
years and have been indicated as a promising strategy for cancer immunotherapy.
Despite their wide applications in the clinical and preclinical stages,
their concomitant viability and efficacy remain major issues. Herein,
a strategy for harnessing regulatory T (Treg) cells is developed as
an actively targeting drug-delivery system to transport drug-loaded
liposomes to the desired tumor sites via conjugating liposomes on
the surface of Treg cells. Under the guidance of tumor-oriented chemokines,
liposome-anchored Treg cells can be leveraged to migrate and infiltrate
the acidic tumor microenvironment, where pH-sensitive liposomes release
the loaded cargos [comprising interleukin-2, programmed cell death
ligand 1 antibody (PD-L1), and imiquimod], provoke dramatic dendritic
cell maturation, block the PD-1/PD-L1 immune-checkpoint, elevate the
frequency of infiltrating CD8+ effector T cells, and collectively
contribute to potent inhibition of in situ and metastatic tumors.
Here, the findings suggest a potential approach that offers a simple,
robust, and safe insight into the tuning of Treg cells as an encouraging
vector for augmenting cancer immunotherapy.
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