Amphiphilic block polymer-based self-assembly of high payload nanoparticles for efficient combinatorial chemo-photodynamic therapy

Drug Deliv. 2020 Nov 16;27(1):1656-1666. doi: 10.1080/10717544.2020.1850921.

Abstract

Combinatorial chemo-photodynamic therapy is regared as effective cancer therapy strategy, which could be realized via multiple nano-drug delivery system. Herein, novel high payload nanoparticles stabilized by amphiphilic block polymer cholesterol-b-poly(ethylene glycol) (PEG)2000 (Chol-PEG2000) were fabricated for loading chemotherapeutic drug 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6). The obtained HCPT/Ce6 NPs showed uniform rod-like morphology with a hydration diameter of 178.9 ± 4.0 nm and excellent stability in aqueous solution. HCPT and Ce6 in the NPs displayed differential release profile, which was benefit for preferentially exerting the photodynamic effect and subsequently enhancing the sensitivity of the cells to HCPT. Under laser irradiation, the NPs demonstrated fantastic in vitro and in vivo anticancer efficiency due to combinational chemo-photodynamic therapy, enhanced cellular uptake effectiveness, and superb intracellular ROS productivity. Besides, the NPs were proved as absent of systemic toxicity. In summary, this nanoparticle delivery system could be hopefully utilized as effective cancer therapy strategy for synergistically exerting combined chemo-photodynamic therapy in clinic.

Keywords: 10-hydroxycamptothecin;; Amphiphilic block polymer;; chlorin e6;; combinatorial chemo-photodynamic therapy;; high payload nanoparticles;.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cell Line, Tumor
  • Chlorophyllides
  • Cholesterol
  • Drug Carriers
  • Drug Delivery Systems*
  • Drug Liberation
  • Female
  • Lasers
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Particle Size
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / therapeutic use
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Porphyrins / administration & dosage
  • Porphyrins / therapeutic use
  • Reactive Oxygen Species

Substances

  • Antineoplastic Agents
  • Chlorophyllides
  • Drug Carriers
  • Photosensitizing Agents
  • Polymers
  • Porphyrins
  • Reactive Oxygen Species
  • hydroxycamptothecinum
  • Polyethylene Glycols
  • phytochlorin
  • Cholesterol
  • Camptothecin

Grants and funding

This work was financially supported by the National Natural Science Foundation of China [no. 22073039], the Natural Science Foundation of Shandong Province of China [no. ZR2018LB023], the Project of Shandong Province Higher Educational Science and Technology Program [no. J18KA071], the Open Project of Shandong Collaborative Innovation Center for Antibody Drugs [no. CIC-AD1831, no. CIC-AD1832], and Tai-Shan Scholar Research Fund of Shandong Province of China [no. 319190201].