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Surface-adaptive zwitterionic nanoparticles for prolonged blood circulation time and enhanced cellular uptake in tumor cells
- Source :
- Acta Biomaterialia. 65:339-348
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Recently, zwitterionic materials have been developed as alternatives to PEG for prolonging the circulation time of nanoparticles without triggering immune responses. However, zwitterionic coatings also hindered the interactions between nanoparticles and tumor cells, leading to less efficient uptake of nanoparticles by cancer cells. Such effect significantly limited the applications of zwitterionic materials for the purposes of drug delivery and the development to novel therapeutic agents. To overcome these issues, surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces were constructed. Owing to the synergistic effect of zwitterionic coatings and micro-phase-separated surfaces, PMPC mixed-shell micelles exhibited the improved blood circulation time compared to single-PEG-shell micelles (PEGSMs) and single-PMPC-shell micelles (PMPCSMs). Moreover, such MSMs can convert their surface to positively charged ones in response to the acidic tumor microenvironment, leading to a significant enhancement in cellular uptake of MSMs by tumor cells. This strategy demonstrated a general approach to enhance the cellular uptake of zwitterionic nanoparticles without compromising their long circulating capability, providing a practical method for improving the tumor-targeting efficiency of particulate drug delivery systems. Statement of Significance Herein we demonstrate a general strategy to integrate non-fouling zwitterionic surface on the nanoparticles without compromising their capability of tumor accumulation, by constructing a surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces. At the blood pH (7.4), PAE chains collapsed to the inner of the shell due to the deprotonation, and the forming micro-phase separation structure was synergistic with zwitterionic surface to prolong the circulation time of MSMs in the blood. While at the tumor sites, PAE was protonated, and the positively charged surface of MSMs enhanced cellular uptake. This self-assembly-based strategy is compatible to other zwitterionic materials, endowing a great flexibility for the construction of responsive drug delivery systems particularly to the novel chemotherapeutic agents.
- Subjects :
- Materials science
Polymers
Surface Properties
Phosphorylcholine
Biomedical Engineering
Nanoparticle
Antineoplastic Agents
Nanotechnology
02 engineering and technology
010402 general chemistry
01 natural sciences
Biochemistry
Micelle
Rats, Sprague-Dawley
Biomaterials
Blood Circulation Time
Drug Delivery Systems
Neoplasms
PEG ratio
Tumor Microenvironment
Animals
Humans
Tissue Distribution
Molecular Biology
Micelles
Ions
Tumor microenvironment
Hep G2 Cells
General Medicine
021001 nanoscience & nanotechnology
0104 chemical sciences
HEK293 Cells
Cancer cell
Drug delivery
Biophysics
Methacrylates
Nanoparticles
Self-assembly
0210 nano-technology
Biotechnology
Subjects
Details
- ISSN :
- 17427061
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Acta Biomaterialia
- Accession number :
- edsair.doi.dedup.....18e675f24b6ad2d216be96c82ec6e583