Targeting to Tumor-Harbored Bacteria for Precision Tumor Therapy

The differential tumor environment guides various antitumor drug delivery strategies for efficient cancer treatment. Here, based on the special bacteria-enriched tumor environment, we report a different drug delivery strategy by targeting bacteria inhabiting tumor sites. With a tissue microarray analysis, it was found that bacteria amounts displayed significant differences between tumor and normal tissues. Bacteria-targeted mesoporous silica nanoparticles decorated with bacterial lipoteichoic acid (LTA) antibody (LTA-MSNs) could precisely target bacteria in tumors and deliver antitumor drugs. By the intravenous administration of bacteria-targeted nanoparticles, we showed in mice with colon cancer, lung cancer, and breast cancer that LTA-MSNs exhibited a high tumor-targeting ability. As a proof-of-concept study, tumor microbes as some of the characteristics of a tumor environment could be utilized as potential targets for tumor targeting. This bacteria-guided tumor-targeting strategy might have great potential in differential drug delivery and cancer treatment

Normalizing Tumor Microenvironment Based on Photosynthetic Abiotic/Biotic Nanoparticles

Tumor hypoxia has attained the status of a core hallmark of cancer that globally affects the entire tumor phenotype. Reversing tumor hypoxia might offer alternative therapeutic opportunities for current anticancer therapies. In this research, a photosynthetic leaf-inspired abiotic/biotic nano-thylakoid (PLANT) system was designed by fusing the thylakoid membrane with synthetic nanoparticles for efficient O₂ generation <i>in vivo</i>. Under 660 nm laser irradiation, the PLANT system exhibited intracellular O₂ generation and the anaerobic respiration of the multicellular tumor spheroid was suppressed by PLANT as well. <i>In vivo</i>, it was found that PLANT could not only normalize the entire metabolic network but also adjust the abnormal structure and function of the tumor vasculature. It was demonstrated that PLANT could significantly enhance the efficacy of phototherapy or antiangiogenesis therapy. This facile approach for normalizing the tumor microenvironment will find great potential in tumor therapy

Enhanced Immunotherapy Based on Photodynamic Therapy for Both Primary and Lung Metastasis Tumor Eradication

Metastasis and recurrence are two unavoidable and intractable problems in cancer therapy, despite various robust therapeutic approaches. Currently, it seems that immunotherapy is an effective approach to solve these problems, but the high heterogeneity of tumor tissue, inefficient presentation of tumor antigen, and deficient targeting ability of therapy usually blunt the efficacy of immunotherapy and hinder its clinical application. Herein, an approach based on combining photodynamic and immunological therapy was designed and developed. We synthesized a chimeric peptide, PpIX-1MT, which integrates photosensitizer PpIX with immune checkpoint inhibitor 1MT <i>via</i> a caspase-responsive peptide sequence, Asp-Glu-Val-Asp (DEVD), to realize a cascaded synergistic effect. The PpIX-1MT peptide could form nanoparticles in PBS and accumulate in tumor areas <i>via</i> the enhanced penetration retention effect. Upon 630 nm light irradiation, the PpIX-1MT nanoparticles produced reactive oxygen species, induced apoptosis of cancer cells, and thus facilitated the expression of caspase-3 and the production of tumor antigens, which could trigger an intense immune response. The subsequently released 1MT upon caspase-3 cleavage could further strengthen the immune system and help to activate CD8⁺ T cells effectively. This cascaded synergistic effect could inhibit both primary and lung metastasis tumor effectively, which may provide the solution for solving tumor recurrence and metastasis clinically

A Biohybrid Lurker-to-Attacker Strategy To Solve Inherent Dilemma of Positively Charged Delivery Nanoparticles

Nonspecific cell attack and rapid in vivo recognition/clearance have been the unsurmountable hurdles against the application of positively charged nanoparticles (pcNPs). The frequently used active targeting approach by grafting specific ligands onto pcNPs suffers from their strong electrostatic interaction with normal cells. We herein put forward a biohybrid strategy to solve this long-standing dilemma in the development of tumor-specific pcNPs. pcNPs are arranged to put on a biological “coat” derived from cancer cell membranes. This design renders pcNPs the high recognition to the homotypic cancer cells with even higher uptake efficiency than the parent pcNPs, while considerably inhibiting the adsorption by biological components, the macrophage capture, and the uptake by the heterotypic cells (e.g., normal and macrophage cells). Encouragingly, the tumor self-targeting by coating pcNPs with the cancer cell membranes proved to be achievable, allowing the role transition to an “attacker” upon reaching the homologous tumor developed from the source cancer cells. This approach paves a facile way to overcome the current limitations for in vivo application of pcNPs