Polymeric Nanoparticles for Mitochondria Targeting Mediated Robust Cancer Therapy

Abstract

Despite all sorts of innovations in medical researches over the past decades, cancer remains a major threat to human health. Mitochondria are essential organelles in eukaryotic cells, and their dysfunctions contribute to numerous diseases including cancers. Mitochondria-targeted cancer therapy, which specifically delivers drugs into the mitochondria, is a promising strategy for enhancing anticancer treatment efficiency. However, owing to their special double-layered membrane system and highly negative potentials, mitochondria remain a challenging target for therapeutic agents to reach and access. Polymeric nanoparticles exceed in cancer therapy ascribed to their unique features including ideal biocompatibility, readily design and synthesis, as well as flexible ligand decoration. Significant efforts have been put forward to develop mitochondria-targeted polymeric nanoparticles. In this review, we focused on the smart design of polymeric nanosystems for mitochondria targeting and summarized the current applications in improving cancer therapy.

Delivery Systems for Mitochondrial Gene Therapy: A Review

“…Their properties, such as easy manipulation of their structure and composition, ability to incorporate ligands, fast and economical production, and biocompatibility, make this type of material one of the most explored in gene therapy. Mitochondrial gene therapy is no exception, with several polymer-based delivery systems being developed that target mitochondria exclusively [ 117 ]. Polymeric systems targeting mitochondria must overcome more barriers than systems that aim to solely cross the cell membrane.…”

“…To this goal, the most commonly applied ligands are lipophilic cations (e.g., triphenylphosphonium, TPP/Dequalinium, DQA/Rhodamine), MTS/MPP ( Figure 4 ), and DNA and RNA aptamers. These ligands are intended to confer mitochondriotropic properties on polyplexes [ 117 , 118 ].…”

A Cascade Targeted and Mitochondrion-Dysfunctional Nanomedicine Capable of Overcoming Drug Resistance in Hepatocellular Carcinoma

“…To maximize the transportation of the active chemotherapeutics toward the target sites, the efficiencies of drug delivery are urged to be primarily considered. , Diverse targeting strategies have been employed for the guidance of nanomedicine to tumor cells or subcellular organelles to seek adequate spatiotemporal drug concentration for cell death. , On the other hand, several sequential targeting strategies have also been devised to further ensure precise accumulation and retention of the intracellular chemotherapeutics in the desirable subcellular organelles. Particularly, mitochondria enriched with mitochondrial DNA (mtDNA) are envisioned to be intriguing targets for DNA damage chemotherapeutics, e.g., cisplatin. − Recently, dual-targeting nanomedicines characterized to possess tumor-targeting and mitochondrion-targeting motifs have been developed to localize the drugs at their pharmaceutic targets . However, detoxification of the intracellular chemotherapeutics would further lead to drug resistance even though there was adequate drug accumulation and retention at the targeted subcellular compartments. − For example, platinum (Pt) is easily deactivated by the overexpressed thiol-containing molecules (especially glutathione, GSH) via ATP-dependent glutathione S-conjugate (GS-X) pumps, resulting in lowered intracellular platinum levels. , Indeed, several strategies have been proposed to protect platinum drugs from GSH deactivation by diminishing the intracellular GSH. , Therefore, a cascade targeted nanomedicine accompanied by antidetoxification facility indicates a tempting potential in the pursuit of maximized intracellular accumulation and retention of active drugs.…”

Hyaluronic Acid-Coated Chitosan Nanoparticles as an Active Targeted Carrier of Alpha Mangostin for Breast Cancer Cells

“…Modification of nanoparticles aims to improve drug targeting through passive or active targeting [ 29 , 30 ]. Passive targeting can enhance the penetration of nanoparticles to the tumor tissue site through an enhanced permeability and retention (EPR) effect [ 31 , 32 , 33 , 34 , 35 ]. Meanwhile, active targeting contains structural modifications and surface functionalization of nanoparticles that lead to more specific targeting capabilities [ 36 , 37 ].…”