PSMA-targeted melanin-like nanoparticles as a multifunctional nanoplatform for prostate cancer theranostics

J Mater Chem B. 2021 Jan 28;9(4):1151-1161. doi: 10.1039/d0tb02576c. Epub 2021 Jan 12.

Abstract

Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of most prostate tumor cells and is considered a promising target for prostate cancer imaging and treatment. It is possible to establish a PSMA-targeted theranostic probe to achieve early diagnosis and treatment of this cancer type. In this contribution, we prepared a multifunctional melanin-like polydopamine (PDA) nanocarrier decorated with a small-molecule PSMA inhibitor, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL). PDA-DCL was then functionalized with perfluoropentane (PFP) and loaded with the photosensitizer chlorin e6 (Ce6) to give Ce6@PDA-DCL-PFP, which was successfully used for ultrasound-guided combined photodynamic/photothermal therapy (PDT/PTT) of prostate cancer. Compared with the corresponding non-targeted probe (Ce6@PDA-PEG-PFP), our targeted probe induced higher cellular uptake in vitro (6.5-fold) and more tumor accumulation in vivo (4.6-fold), suggesting strong active targeting capacity. Meanwhile, this new nanoplatform significantly enhanced the ultrasound contrast signal at the tumor site in vivo, thus facilitating precise and real-time detection of the tumor. In addition, this Ce6-loaded PDA nanoplatform produced a synergistic effect of PDT and PTT under 660 nm and 808 nm irradiation, inducing a more efficient killing effect compared with the individual therapy in vitro and in vivo. Furthermore, the tumor in the targeted group was more effectively suppressed than that in the non-targeted group under the same irradiation condition. This multifunctional probe may hold great potential for precise and early theranostics of prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Chlorophyllides
  • Drug Carriers / chemistry
  • Drug Screening Assays, Antitumor
  • Fluorocarbons / chemistry
  • Fluorocarbons / pharmacology
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology
  • Infrared Rays
  • Male
  • Nanoparticles / chemistry*
  • Particle Size
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Polymers / chemistry
  • Polymers / pharmacology
  • Porphyrins / chemistry
  • Porphyrins / pharmacology
  • Prostate-Specific Antigen / analysis*
  • Prostate-Specific Antigen / antagonists & inhibitors
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Surface Properties
  • Theranostic Nanomedicine*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Chlorophyllides
  • Drug Carriers
  • Fluorocarbons
  • Indoles
  • Photosensitizing Agents
  • Polymers
  • Porphyrins
  • polydopamine
  • phytochlorin
  • perfluoropentane
  • Prostate-Specific Antigen