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Cholesterol-Modified Dendrimers for Constructing a Tumor Microenvironment-Responsive Drug Delivery System
Ke-Fei Xu1, Hao-Ran Jia1, Ya-Xuan Zhu1
1State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P. R. China.
ACS Biomaterials Science & Engineering
|January 6, 2021
Summary
Poly(amidoamine) dendrimers modified with poly(ethylene glycol)-cholesterol form nanoparticles for drug delivery. These nanozymes produce oxygen to enhance photodynamic therapy, showing promising tumor treatment in vivo.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Materials Science
Background:
- Poly(amidoamine) (PAMAM) dendrimers serve as effective templates for nanoparticle synthesis.
- Surface modification of PAMAM dendrimers with poly(ethylene glycol)-cholesterol yields self-assembled nanoparticles (DPC NPs) with enhanced cellular uptake.
- Dendrimer-based nanoparticles offer hydrophobic cores suitable for encapsulating therapeutic agents.
Purpose of the Study:
- To develop novel drug carriers for photodynamic therapy (PDT) using modified PAMAM dendrimers.
- To enhance PDT efficacy in hypoxic tumor environments by incorporating oxygen-generating capabilities.
- To create smart nanozymes for targeted drug delivery and improved cancer treatment.
Main Methods:
- Self-assembly of amine-terminated generation 4 PAMAM dendrimers with poly(ethylene glycol)-cholesterol to form DPC NPs.
- Encapsulation of chlorin e6 (Ce6) photosensitizer into DPC NPs to create DPCC NPs for PDT.
- In situ synthesis of manganese dioxide (MnO2) within DPCC NPs to form Ce6/MnO2@DPC NPs (DPCCM NPs) with nanozyme activity.
- In vivo imaging using cyanine7-conjugated DPCCM NPs to assess tumor accumulation.
Main Results:
- Cellular uptake of DPC NPs demonstrated a cholesterol-content-dependent increase.
- DPCCM NPs catalyzed hydrogen peroxide (H2O2) to produce oxygen, enhancing PDT efficacy under laser irradiation.
- In vivo studies showed excellent tumor accumulation of DPCCM NPs after intravenous administration.
- Satisfactory in vivo antitumor therapeutic outcomes and good biosafety were observed.
Conclusions:
- The developed DPCCM NPs represent a novel strategy for improving drug cellular uptake and enhancing PDT in hypoxic tumors.
- This work introduces a method for synthesizing smart nanozymes based on dendrimers for targeted cancer therapy.
- The findings suggest a promising approach for developing advanced nano-therapeutics with combined drug delivery and oxygen-generating properties.
