Intelligent Responsive Nanoparticles with Multilevel Triggered Drug Penetration for Tumor Photochemotherapy.

Nanomedicines have contradictory size requirements to overcome systemic barriers and penetrate the tumor extracellular matrix (ECM). Larger-sized nanoparticles (50-200 nm) exhibit prolonged blood circulation half-life and improved tumor enrichment, while small-sized nanoparticles (4-20 nm) easily penetrate deep tumor tissues. Therefore, the development of intelligent responsive nanomedicine systems can not only increase nanodrug tumor accumulation but also improve their penetration into the ECM. Herein, we propose an intelligent responsive nanoparticle triggered by near-infrared light (NIR). The nanoparticle was constructed by a temperature-sensitive liposome (TSL) encapsulating ultrasmall melanin nanoparticles (MNPs) loaded with doxorubicin (MNP/doxorubicin (DOX)@TSL). When exposed to NIR irradiation, the tailor-made nanoparticles not only effectively ablated the tumor cells around blood vessels but also destroyed the structural integrity and released loaded ultrasmall MNP/DOX (<10 nm) to promote deep tumor penetration and enhance interior tumor cell killing. This NIR-triggered intelligent nanoparticle successfully integrated photothermal therapy (PTT) for perivascular tumor cells and chemotherapy for deep tumor cell inhibition. The in vivo results showed remarkable tumor regression in 4T1 breast tumor-bearing mice by 74.2%. This controllable size switchable nanosystem with efficient tumor accumulation and penetration has shown great potential in improving synergistic antitumor effects of photochemotherapy.

Biogenetic Vesicle-Based Cancer Vaccines with Tunable Surface Potential and Immune Potency.

Cancer vaccines are designed to motivate antigen-specific immune responses and facilitate tumor regression with minimal side effects. To fully exert the potential of vaccines, rationally designed formulations that effectively deliver antigens and trigger potent immune reactions are urgently needed. This study demonstrates a simple and controllable vaccine-developing strategy that assembles tumor antigens into bacterial outer membrane vesicles (OMVs), natural delivery vehicles with intrinsic immune adjuvant properties, via electrostatic interaction. This OMV-delivered vaccine (OMVax) stimulated both innate and adaptive immune responses, leading to enhanced metastasis inhibition and prolonged survival of tumor-bearing mice. Moreover, the influence of different surface charged OMVax on antitumor immunity activation is investigated and declined immune response activation occurred with increased positive surface charge. Together, these findings suggest a simple vaccine formulation that can be enhanced by optimizing the surface charges of vaccine formulations.