Intracellular Peptide Self-Assembly: A Biomimetic Approach for in Situ Nanodrug Preparation

Abstract

Most nanodrugs are preprepared by encapsulating or loading the drugs with nanocarriers (e.g., dendrimers, liposomes, micelles, and polymeric nanoparticles). However, besides the low bioavailability and fast excretion of the nanodrugs in vivo, nanocarriers often exhibit in vitro and in vivo cytotoxicity, oxidative stress, and inflammation. Self-assembly is a ubiquitous process in biology where it plays important roles and underlies the formation of a wide variety of complex biological structures. Inspired by some cellular nanostructures (e.g., actin filaments, microtubules, vesicles, and micelles) in biological systems which are formed via molecular self-assembly, in recent decades, scientists have utilized self-assembly of oligomeric peptide under specific physiological or pathological environments to in situ construct nanodrugs for lesion-targeted therapies. On one hand, peptide-based nanodrugs always have some excellent intrinsic chemical (specificity, intrinsic bioactivity, biodegradability) and physical (small size, conformation) properties. On the other hand, stimuli-regulated intracellular self-assembly of nanodrugs is quite an efficient way to accumulate the drugs in lesion location and can realize an in situ slow release of the drugs. In this review article, we provided an overview on recent design principles for intracellular peptide self-assembly and illustrate how these principles have been applied for the in situ preparation of nanodrugs at the lesion location. In the last part, we list some challenges underlying this strategy and their possible solutions. Moreover, we envision the future possible theranostic applications of this strategy.

Increasing Photothermal Efficacy by Simultaneous Intra‐ and Intermolecular Fluorescence Quenching

“…Unfortunately, there were still a large portion of 1 and 1‐Fmoc stuck in other main organs (lung, kidneys, colon, stomach) even at 48 h post injection (Figure S19b,c Supporting Information). This might be attributed to the sodium‐dependent multivitamin transporter (SMVT) in the gastrointestinal organs for biotin uptake, and bring the risk of long‐term toxicity to the main organs . Thus, intratumoral injection was chosen for the delivery of our PTAs to the tumor sites.…”

“…Thus, these nanosized PTAs will achieve the excellent pharmacokinetic properties of nanomaterials such as long circulation time, high metabolic stability, etc . However, those premade nanoscale PTAs will inevitably confront with the fundamental problems of nanomaterials such as difficulties in large scale fabrication with good reproducibility, unintended uptake, and retention in reticuloendothelial system organs, or nanotoxicity induced by their in vivo long‐term metabolism . Meanwhile, recent meta‐analysis shows that, in average, only 0.7% of the administered nanodrug is delivered to the tumor, while the rest is accumulated in healthy organs 11a,19…”

Peptide-Decorated Supramolecules for Subcellular Targeted Cancer Therapy: Recent Advances

“…As one of the most essential organelles, the implementation of non-drug-loaded peptide nanoassemblies for mitochondriatargeted therapy has attracted increasing attention (Jeena et al, 2017;Du et al, 2018;Li et al, 2018;Liu et al, 2018;. Given that the elimination of cancer cells was conducted by the nanoassemblies themselves without using drugs, it undoubtedly avoids MDR.…”

Peptide‐Based Supramolecular Nanodrugs as a New Generation of Therapeutic Toolboxes against Cancer

“…[9] Through the supramolecular self-assembly strategy, a number of supramolecular nanodrugs have been constructed by molecular building blocks via noncovalent intermolecular interactions. [11] These therapeutic agents not only possess characteristics of peptides but also can selfassemble into special structures with unique treatment effects. Based on the advantages of peptide self-assembly mentioned above, many peptide-based nanodrugs have been constructed as therapeutic toolboxes for cancer therapy.…”

“…Based on the advantages of peptide self-assembly mentioned above, many peptide-based nanodrugs have been constructed as therapeutic toolboxes for cancer therapy. [11] These therapeutic agents not only possess characteristics of peptides but also can selfassemble into special structures with unique treatment effects. On the one hand, diverse peptide-based nanostructures can be used as carriers to protect hydrophobic drugs until they reach the target lesions, reducing leakage and enhancing therapeutic effects.…”