Self-Delivery Nanoplatform Based on Amphiphilic Apoptosis Peptide for Precise Mitochondria-Targeting Photothermal Therapy

Abstract

Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondriatargeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

Synthesis of a catalytic nanomaterial from polypyrrole and a pro-apoptotic peptide to target mitochondria for multimodal cancer therapy

“…With the purpose of facilitating cellular uptake, the KLA peptide can be fused with cell-penetrating moieties or ligands, encapsulated into liposomes, or complexed with polyelectrolytes. 11,12 After internalization into cancer cells, KLA preferentially interacts with the negatively charged mitochondrial membrane, causing disruption in mitochondrial membrane potential and resulting in cell death. 13,14 Besides, the integration of the KLA peptide with nanomaterials with multi-functionalities may offer a unique approach for the design of KLA therapeutic platforms with mitochondria-targeting and multimodal therapeutic activities for synergistic cancer therapy.…”

Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy

“…Recently, phototherapy , based on the photochemical effect has become a favored approach among researchers due to its noninvasive nature, high spatiotemporal selectivity, and excellent controllability. − By light irradiation, photodynamic therapy (PDT) can generate a large amount of reactive oxygen species (ROS), , which destroy the structure of tumor cells through interaction with a variety of biological macromolecules, thereby eliminating the tumor cells. Simultaneously, the immunogenic cell death (ICD) of tumor cells mediated by PDT initiates the antitumor immune response. − In this process, CRT, a prophagocytic signaling molecule that releases an “eat me” signal, translocates from the endoplasmic reticulum to the tumor cell membrane and promotes phagocytosis of tumor cells by macrophages. , Meanwhile, the protein high mobility group box 1 (HMGB1) is released from the nucleus of tumor cells, which can promote the maturation of DCs and enhance the efficiency of tumor antigen presentation. , Adenosine triphosphate (ATP) is secreted from the tumor cytoplasm, which can enhance the infiltration of CTLs into the tumor microenvironment …”