Smart nanoplatform for sequential drug release and enhanced chemo-thermal effect of dual drug loaded gold nanorod vesicles for cancer therapy

J Nanobiotechnology. 2019 Mar 27;17(1):44. doi: 10.1186/s12951-019-0473-3.

Abstract

Background: The combination of multiple chemotherapeutics has been used in the clinic for enhanced cancer chemotherapy, however, frequent relapse, chemo-resistance and side effects remains therapeutic hurdles. Thus, the development of co-delivery system with enhanced targeting and synergistic different modal treatments has been proposed as promising strategies for intensive improvement of the therapeutic outcomes.

Results: We fabricated a nanocarrier based on gold nanorods (Au NRs), cRGD peptide-modified and multi-stimuli-responsive paclitaxel (PTX) and curcumin (CUR) release for synergistic anticancer effect and chemo-photothermal therapy (PTX/CUR/Au NRs@cRGD). The specific banding of cRGD to αvβ3 integrin receptor on the tumor cell surfaces facilitated the endocytosis of PTX/CUR/Au NRs@cRGD, and the near-infrared ray (NIR) further enhanced the drug release and chemotherapeutical efficiency. Compared to single drug, single model treatment or undecorated-PTX/CUR/Au NRs, the PTX/CUR/Au NRs@cRGD with a mild NIR showed significantly enhanced apoptosis and S phase arrest in three cancer cell lines in vitro, and improved drug accumulation in tumor sites as well as tumor growth inhibition in vivo.

Conclusions: The tumor targeted chemo-photothermal therapy with the synergistic effect of dual drugs provided a versatile strategy for precise cancer therapy.

Keywords: Combination therapy; Dual drug; NIR photothermal effect; Sequential drug release; Stimuli-responsive; Synergistic effect.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Curcumin / administration & dosage*
  • Curcumin / chemistry
  • Drug Carriers / chemistry*
  • Drug Liberation*
  • Gold / chemistry*
  • Hep G2 Cells
  • Humans
  • Infrared Rays
  • Integrin alphaVbeta3 / metabolism
  • KB Cells
  • Mice, Inbred BALB C
  • Nanotubes / chemistry*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Particle Size
  • Peptides, Cyclic / metabolism
  • Phototherapy / methods
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Integrin alphaVbeta3
  • Peptides, Cyclic
  • cyclic arginine-glycine-aspartic acid peptide
  • Gold
  • Curcumin
  • Paclitaxel