Portfolio Targeting Strategy To Realize the Assembly and Membrane Fusion-Mediated Delivery of Gold Nanoparticles to Mitochondria for Enhanced NIR Photothermal Therapies

Abstract

Targeting mitochondria has always been a challenging goal for therapeutic nanoparticle agents due to their heterotypic features and size, which usually lead to a lysosome/endosome endocytosis pathway. To overcome this limitation, in this work, a portfolio targeting strategy combining a small targeting molecule with a biomembrane was developed. Modification of small targeting molecule H 2 N-TPP on gold nanoparticles (GNPs) could not only facilitate the mitochondrial targeting but could also induce gold nanoparticle assembly. Therefore, the GNPs were endowed with good absorption and photothermal conversion abilities in the near-infrared (NIR) region. Meanwhile, a biomimetic strategy was adopted by wrapping the gold nanoparticle assembly (GNA) with cancer cell membranes (CCMs), which helped the GNA enter the prostatic cancer cell via a homotypic membranefusion process to avoid being trapped in endosomes/lysosomes. Thereafter, the GNA remaining in the cytoplasm could reach mitochondria more efficiently via guidance from H 2 N-TPP molecules. This "biomembrane−small molecule" combination targeting process was evidenced by fluorescence microscopy, and the highly efficient photothermal ablation of prostatic tumors in vivo was demonstrated. This portfolio targeting strategy could be extended to various nanodrugs/agents to realize an accurate subcellular targeting efficiency for cancer treatments or cell detections.

Rapid Mitochondria Targeting by Arginine-Terminated, Sub-10 nm Nanoprobe via Direct Cell Membrane Penetration

“…First, mitochondria labeling by the designed nanoprobe is rapid and similar to conventional molecular probes. For example, all the reported nanoprobes require several hours (typically between 4 and 24 h) for mitochondria labeling, − and the peptide/macromolecule-based probe requires 1–5 h for such labeling , (see Table S1). Such longer time requirements are linked to the endocytic uptake processes followed by intracellular processing .…”

“…Mitochondria targeting materials offer selective imaging/monitoring, drug delivery, and therapy application. − Designed materials include small molecule, ,− liposome, peptide, polymer–micelle, dendrimer, and nanoparticle. − Among them, polymer micelle/liposome/nanoparticle has the advantage as a carrier for therapeutic application, as more drugs can be loaded . In addition, nanoparticles with an optical property have the potential for imaging and photothermal therapy .…”

Multifunctional Mitochondria-Targeting Nanosystems for Enhanced Anticancer Efficacy

“…Although gold nanoparticles have been confirmed to be excellent drug delivery platforms for many drugs, they are not desirable vehicles of PTT agents because of their poor photothermal conversion efficiency and their poor endosome/lysosome escape capability ( Feng et al, 2017 ; Zhang et al, 2019 ). Herein, Ning et al (2020) designed a photothermal therapeutic “shell-core” nanosystem CCM-TPP-GNA, where a mitochondrial targeting gold nanoparticle assembly (TPP-GNA) served as the core and PC-3 cancer cell membrane (CCM) served as the shell for enhanced endosome/lysosome escape. In their study, the gold nanoparticles were endowed with mitochondria-targeting ability, excellent absorption, and efficient photothermal conversion capacity in the NIR region by the decoration with synthesized TPP derivatives.…”

A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics

“… 22 Emerging nanobiotechnology, cancer cell membrane (CCM)-coated nanoparticles, has been applied in various therapeutic and diagnostic practices, including but not limited to drug delivery. 23 , 24 , 25 , 26 , 27 , 28 Such a bionic nanotechnology uses CCMs with unique biological components, and has been effectively combined with different types of nanoparticles to improve targeted delivery. 29 , 30 , 31 The efficient enrichment of nanoparticles at the tumor site can be attributed to homologous targeting and immune escape.…”