Advancing nanotechnology for neoantigen-based cancer theranostics.

Neoantigens play a pivotal role in the field of tumour therapy, encompassing the stimulation of anti-tumour immune response and the enhancement of tumour targeting capability. Nonetheless, numerous factors directly influence the effectiveness of neoantigens in bolstering anti-tumour immune responses, including neoantigen quantity and specificity, uptake rates by antigen-presenting cells (APCs), residence duration within the tumour microenvironment (TME), and their ability to facilitate the maturation of APCs for immune response activation. Nanotechnology assumes a significant role in several aspects, including facilitating neoantigen release, promoting neoantigen delivery to antigen-presenting cells, augmenting neoantigen uptake by dendritic cells, shielding neoantigens from protease degradation, and optimizing interactions between neoantigens and the immune system. Consequently, the development of nanotechnology synergistically enhances the efficacy of neoantigens in cancer theranostics. In this review, we provide an overview of neoantigen sources, the mechanisms of neoantigen-induced immune responses, and the evolution of precision neoantigen-based nanomedicine. This encompasses various therapeutic modalities, such as neoantigen-based immunotherapy, phototherapy, radiotherapy, chemotherapy, chemodynamic therapy, and other strategies tailored to augment precision in cancer therapeutics. We also discuss the current challenges and prospects in the application of neoantigen-based precision nanomedicine, aiming to expedite its clinical translation.

Biomimetic Yolk-Shell Nanocatalysts for Activatable Dual-Modal-Image-Guided Triple-Augmented Chemodynamic Therapy of Cancer.

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (·OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on ·OH, low intracellular H2O2 level, and low reaction rate, resulting in unsatisfactory efficacy. Here, a cancer cell membrane (CM)-camouflaged Au nanorod core/mesoporous MnO2 shell yolk-shell nanocatalyst embedded with glucose oxidase (GOD) and Dox (denoted as AMGDC) is constructed for synergistic triple-augmented CDT and chemotherapy of tumor under MRI/PAI guidance. Benefiting from the homologous adhesion and immune escaping property of the cancer CM, the nanocatalysts can target tumor and gradually accumulate in tumor site. For triple-augmented CDT, first, the MnO2 shell reacts with intratumoral GSH to generate Mn2+ and glutathione disulfide, which achieves Fenton-like ion delivery and weakening of GSH-mediated scavenging effect, leading to GSH depletion-enhanced CDT. Second, the intratumoral glucose can be oxidized to H2O2 and gluconic acid by GOD, achieving supplementary H2O2-enhanced CDT. Next, the AuNRs absorbing in NIR-II elevate the local tumor temperature upon NIR-II laser irradiation, achieving photothermal-enhanced CDT. Dox is rapidly released for adjuvant chemotherapy due to responsive degradation of MnO2 shell. Moreover, GSH-activated PAI/MRI can be used to monitor CDT process. This study provides a great paradigm for enhancing CDT-mediated antitumor efficacy.