Direct Cellular Delivery of Exogenous Genetic Material and Protein via Colloidal Nano-Assemblies with Biopolymer

Abstract

Direct cytosolic delivery of large biomolecules that bypass the endocytic pathways is a promising strategy for therapeutic applications. Recent works have shown that small-molecule, nanoparticle, and polymer-based carriers can be designed for direct cytosolic delivery. It has been shown that the specific surface chemistry of the carrier, nanoscale assembly between the carrier and cargo molecule, good colloidal stability, and low surface charge of the nano-assembly are critical for non-endocytic uptake processes. Here we report a guanidinium-terminated polyaspartic acid micelle for direct cytosolic delivery of protein and DNA. The polymer delivers the protein/DNA directly to the cytosol by forming a nano-assembly, and it is observed that <200 nm size of colloidal assembly with near-zero surface charge is critical for efficient cytosolic delivery. This work shows the importance of size and colloidal property of the nano-assembly for carrier-based cytosolic delivery of large biomolecules.

Nuclear Transport of the Molecular Drug via Nanocarrier-Based Nonendocytic Cellular Uptake

“…The chemical composition and structure of the nanocarrier are shown in Figure a. It is based on a polyaspartic acid-based polymer micelle . It has been synthesized by converting l -aspartic acid into polyaspartimide and then reacted with oleylamine, amino-benzyl guanidinium, and amino-chlorocholine ligand in a stepwise manner (see Experimental Section and Figures S1–S7, Supporting Information).…”

Recent progress in nanomedicine-mediated cytosolic delivery

“…7 ). 51 The vehicle displayed a strong positive charge at the surface, resulting in nano-assembly via electrostatic interactions with both DNA and proteins. The colloidal stability of the nano-assembly was maintained even in DMEM for 24 hours.…”

Functionalized Peptide-Based Nanoparticles for Targeted Cancer Nanotherapeutics: A State-of-the-Art Review

“…In addition to this, several parameters such as surface area and molar concentration also influence the accurate assessment of such drugs. Unfortunately, the obstacles for quantification are progressively increasing as the surface area has gone from single particle to complex nanoassemblies. − …”

“…Unfortunately, the obstacles for quantification are progressively increasing as the surface area has gone from single particle to complex nanoassemblies. 94 − 97 …”