Photodynamic therapy (PDT) is a promising anticancer treatment and is clinically approved for different types of tumors. However, current PDT suffers several obstacles, including its neutralization by excess glutathione (GSH) in the tumor tissue and its strongly proangiogenic tumor response. In this work, a biomimic, multifunctional nanoparticle‐based PDT agent, combining a tumor‐targeted photosensitizer with GSH scavenging and antiangiogenesis therapy, is developed. A porphyrinic Zr–metal–organic framework nanoparticle is used simultaneously as the photosensitizer and the delivery vehicle of vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib. The core nanoparticles are wrapped in MnO2 to consume the intratumoral GSH and then decorated with a tumor cell membrane camouflage. After intravenous administration, the nanoparticles selectively accumulate in tumor through homotypic targeting mediated by the biomimic decoration, and the combination of enhanced PDT and antiangiogenic drug significantly improves their tumor inhibition efficiency. This study provides an integrated solution for mechanism‐based enhancement of PDT and demonstrates the encouraging potential for multifunctional nanosystem applicable for tumor therapy.
Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on Escherichia coli cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8+ T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer.
Home-based pulmonary rehabilitation programs represent effective therapeutic intervention approaches for relieving COPD-associated respiratory symptoms and improving HRQoL and exercise capacity. Rigorously designed, large-scale RCTs are still needed to identify an optimal standard home-based pulmonary rehabilitation program.
The
complete regression of residual tumors after photothermal therapy
(PTT) depends on the activation and recognition of the immune system.
However, the inevitable local inflammation after PTT in residual tumor
recruits abundant abnormal immune cells, especially the tumor-associated
macrophages (TAMs) which further promote immune escape and survival
of the remaining tumor cells, resulting in the tumor recurrence and
progression. To solve this problem, herein we explored biomimetic
nanoparticles carrying repolarization agent of TAMs to remodel the
post-PTT inflammatory microenvironment. The polydopamine nanoparticles
were used simultaneously as photothermal transduction agents to ablate
tumor cells and the delivery vehicles for TMP195 which can repolarize
the M2-like TAMs into an antitumor phenotype. In addition, a biomimetic
decoration of macrophage membrane coating was designed to endow nanoparticles
the ability to actively target the tumor site after PTT mediated by
inflammation-mediated chemotaxis. In the breast tumor model, these
biomimetic nanoparticles with immune-modulating ability significantly
elevated the levels of M1-like TAMs, ultimately resulting in a tumor-elimination
rate of 60%, increased from 10% after PTT. This synergistic treatment
strategy of PTT and TAMs repolarization provides a promising approach
to address the deteriorated tumor microenvironment after PTT and proposes
a more effective way for combinational treatment option in clinic.
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