Safe and effective strategies are urgently needed to fight against the life‐threatening diseases of various cancers. However, traditional therapeutic modalities, such as radiotherapy, chemotherapy and surgery, exhibit suboptimal efficacy for malignant tumors owing to the serious side effects, drug resistance and even relapse. Phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), are emerging therapeutic strategies for localized tumor inhibition, which can produce a large amount of reactive oxygen species (ROS) or elevate the temperature to initiate cell death by non‐invasive irradiation. In consideration of the poor bioavailability of phototherapy agents (PTAs), lots of drug delivery systems have been developed to enhance the tumor targeted delivery. Nevertheless, the carriers of drug delivery systems inevitably bring biosafety concerns on account of their metabolism, degradation, and accumulation. Of note, carrier‐free nanomedicine attracts great attention for clinical translation with synergistic antitumor effect, which is characterized by high drug loading, simplified synthetic method and good biocompatibility. In this review, the latest advances of phototherapy with various carrier‐free nanomedicines are summarized, which may provide a new paradigm for the future development of nanomedicine and tumor precision therapy.
Tumor-associated macrophages (TAMs) are the most abundant
immune
cells in solid tumor tissues, which restrict antitumor immunity by
releasing tumor-supporting cytokines and attenuating phagocytosis
behaviors. In this work, a chimeric peptide engineered bioregulator
(ChiP-RS) is constructed for tumor immunotherapy through macrophage
polarization and phagocytosis restoration. ChiP-RS is fabricated by
utilizing macrophage-targeting chimeric peptide (ChiP) to load Toll-like
receptor agonists (R848) and Src homology 2 (SH2) domain-containing
protein tyrosine phosphatase 2 (SHP-2) inhibitor (SHP099). Among which,
ChiP-RS prefers to be internalized by TAMs, repolarizing M2 macrophages
into M1 macrophages to reverse the immunosuppressive microenvironment.
In addition, SHP-2 can be downregulated to promote phagocytotic elimination
behaviors of M1 macrophages, which will also activate T cell-based
antitumor immunity for metastatic tumor therapy. In vitro and in vivo findings demonstrate a superior suppression
effect of ChiP-RS against metastatic tumors without systemic side
effects. Such a simple but effective nanoplatform provides sophisticated
synergism for immunotherapy, which may facilitate the development
of translational nanomedicine for metastatic tumor treatment.
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