Size-Transformable Hyaluronan Stacked Self-Assembling Peptide Nanoparticles for Improved Transcellular Tumor Penetration and Photo-Chemo Combination Therapy

Zhaoqing Cong, Lu Zhang, Si Qi Ma, Kit S. Lam, Fei Fei Yang, Yong Hong Liao

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Size-transformable nanomedicine has the potential to overcome systemic and local barriers, leading to efficient accumulation and penetration throughout the tumor tissue. However, the design of this type of nanomedicine was seldom based on active targeting and intracellular size transformation. Here, we report an intracellular size-transformable nanosystem, in which small and positively charged nanoparticles (<30 nm) prepared from the self-assembly of an amphiphilic hexadecapeptide derivative was coated by folic acid- and dopamine-decorated hyaluronan (HA) to form large and negatively charged nanoparticles (∼130 nm). This nanosystem has been proven to improve the blood circulation half-life of the drug and prevent premature intravascular drug leakage from the nanocarrier. Once accumulated in the tumor, the nanoparticles were prone to HA- and folic acid-mediated cellular uptake, followed by intracellular size transformation and discharge of transformed small nanoparticles. The size-transformable nanosystem facilitated the transcytosis-mediated tumor penetration and improved the internalization of nanoparticles by cells and the intracellular release of 7-ethyl-10 hydroxycamptothecin. With an indocyanine green derivative as the intrinsic component of the amphiphilic polymer, the nanosystem has exhibited additional theranostic functions: photoacoustic imaging, NIR-laser-induced drug release, and synergistic chemotherapy and phototherapy, leading to a 50% complete cure rate in a subcutaneous B16 melanoma model. This nanosystem with multimodalities and efficient tumor penetration has shown potentials in improving anticancer efficacy.

Original languageEnglish (US)
Pages (from-to)1958-1970
Number of pages13
JournalACS Nano
Volume14
Issue number2
DOIs
StatePublished - Feb 25 2020

Keywords

  • combination therapy
  • peptide nanoparticle
  • transcellular
  • transformable
  • tumor penetration

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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