Abstract
The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This “four-in-one” nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.
Highlights
In the past few years, many treatments [1,2,3,4], such as chemotherapy, radiotherapy, gene therapy, phototherapy and immunotherapy, have been widely investigated, cancers cannot be cured by any monotherapy regimens in many cases
Nanoscale drug delivery systems (10–200 nm) have been verified to augment the anticancer activities of drugs, as they enrich in solid tumors through the enhanced permeability and retention (EPR) effect [13,14,15,16,17,18,19]
Liposomes can load different kinds of drugs in both hydrophobic bilayer and hydrophilic cavity [20,21,22], but they suffer from low stability and uncontrollable drug release
Summary
In the past few years, many treatments [1,2,3,4], such as chemotherapy, radiotherapy, gene therapy, phototherapy and immunotherapy, have been widely investigated, cancers cannot be cured by any monotherapy regimens in many cases. PDA-coated nanocarriers could achieve tumor-targeted dual drug delivery and synergistic chemo-photothermal therapy, which has not yet been reported for cancer therapy. We report on the performance of a PDA-coated “four-in-one” polymeric nanoplatform for targeted dual drug delivery and synergistic chemo and photothermal therapy of breast cancer. PDA-coated NPs can adsorb the anticancer drug DOX, thereby enabling the simultaneous loading of DTX (which acts on microtubules) and DOX (which acts on nuclei) After their intravenous injection, targeting NPs accumulate in tumor sites, become ingested by tumor cells and provide chemo–photothermal therapy under NIR irradiation
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