Design and construction of IR780- and EGCG-based and mitochondrial targeting nanoparticles and their application in tumor chemo-phototherapy

J Mater Chem B. 2021 Dec 15;9(48):9932-9945. doi: 10.1039/d1tb01899j.

Abstract

An integration combination of phototherapy and chemotherapy to treat carcinoma, solving the inner limitation of individual-modal chemical agent-based therapy or phototherapy, emerges to be a strategy with high prospects for achieving synergistic curative effects. The dye IR780-iodide (IR780) close to infrared radiation is a phototherapy agent with high prospects. However, it is limited in its clinical applications due to poor solubility in water. While epigallocatechin-3-gallate (EGCG), naturally resourced green tea polyphenol, has been extensively proven with intrinsic antitumor activity, but it is largely restricted by its low bioavailability in vivo. Hence, novel multiple-function nanoparticles comprising hyaluronic acid (HA) and IR780 were proposed to deliver EGCG, defined as EGCG@THSI nano-scale particles (EGCG@THSI NPs), thereby rapidly solving limitations of EGCG and IR780. Amphiphilic nano-scale carrier was prepared by triphenylphosphine (TPP), hyaluronic acid (HA), cystamine, and IR780, termed as TPP-HA-SS-IR780, and EGCG was loaded into the amphiphilic copolymer by self-assembly. TPP-HA-SS-IR780 endowed the as-synthesized EGCG@THSI NPs with excellent TPP-mediated mitochondrial-targeted and glutathione-triggered rapid drug release properties. As impacted by the integration of phototherapy and chemotherapy, the EGCG@THSI NPs under NIR laser irradiation showed a prominent anti-tumor effect. Taken together, this study presented a multiple-function nano-scale carrier platform with high prospects in improving the therapeutic efficacy of anti-carcinoma drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology*
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Iodides / chemistry
  • Iodides / pharmacology*
  • Materials Testing
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Molecular Structure
  • Nanoparticles / chemistry
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Photothermal Therapy*
  • Zebrafish

Substances

  • 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
  • Antineoplastic Agents
  • Fluorescent Dyes
  • Indoles
  • Iodides
  • Photosensitizing Agents
  • Catechin
  • epigallocatechin gallate