Novel Core-Interlayer-Shell DOX/ZnPc Co-loaded MSNs@ pH-Sensitive CaP@PEGylated Liposome for Enhanced Synergetic Chemo-Photodynamic Therapy

Pharm Res. 2018 Feb 8;35(3):57. doi: 10.1007/s11095-017-2295-z.

Abstract

Purpose: This work was intended to develop novel doxorubicin (DOX)/zinc (II) phthalocyanine (ZnPc) co-loaded mesoporous silica (MSNs)@ calcium phosphate (CaP)@PEGylated liposome nanoparticles (NPs) that could efficiently achieve collaborative anticancer therapy by the combination of photodynamic therapy (PDT) and chemotherapy. The interlayer of CaP could be utilized to achieve pH-triggered controllable drug release, promote the cellular uptake, and induce cell apoptosis to further enhance the anticancer effects.

Methods: MSNs were first synthesized as core particles in which the pores were diffusion-filled with DOX, then the cores were coated by CaP followed by the liposome encapsulation with ZnPc to form the final DOX/ZnPc co-loaded MSNs@CaP@PEGylated liposome.

Results: A core-interlayer-shell MSNs@CaP@PEGylated liposomes was developed as a multifunctional theranostic nanoplatform. In vitro experiment indicated that CaP could not only achieve pH-triggered controllable drug release, promote the cellular uptake of the NPs, but also generate high osmotic pressure in the endo/lysosomes to induce cell apoptosis. Besides, the chemotherapy using DOX and PDT effect was achieved by the photosensitizer ZnPc. Furthermore, the MSNs@CaP@PEGylated liposomes showed outstanding tumor-targeting ability by enhanced permeability and retention (EPR) effect.

Conclusions: The novel prepared MSNs@CaP@PEGylated liposomes could serve as a promising multifunctional theranostic nanoplatform in anticancer treatment by synergic chemo-PDT and superior tumor-targeting ability.

Keywords: calcium phosphate; liposome; photodynamic therapy; synergistic treatment; tumor targeting.

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Apoptosis / drug effects
  • Calcium Phosphates / chemistry
  • Combined Modality Therapy / methods
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Drug Compounding / methods
  • Drug Liberation
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Indoles / administration & dosage
  • Indoles / pharmacokinetics
  • Isoindoles
  • Liposomes
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / pharmacokinetics
  • Photochemotherapy / methods
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / pharmacokinetics
  • Polyethylene Glycols / chemistry
  • Silicates / chemistry
  • Theranostic Nanomedicine / methods*
  • Zinc Compounds

Substances

  • Antibiotics, Antineoplastic
  • Calcium Phosphates
  • Delayed-Action Preparations
  • Indoles
  • Isoindoles
  • Liposomes
  • Organometallic Compounds
  • Photosensitizing Agents
  • Silicates
  • Zinc Compounds
  • Zn(II)-phthalocyanine
  • Polyethylene Glycols
  • Doxorubicin
  • calcium phosphate