Folate-receptor-targeted laser-activable poly(lactide-<em>co</em>-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy

Abstract

BackgroundCancer is one of the most serious threats to human health. Precision medicine is an innovative approach to treatment, as part of which theranostic nanomedicine has been studied extensively. However, the required biocompatibility and substantial cost for the approval of nanomedicines hinder their clinical translation.PurposeWe designed a novel type of theranostic nanoparticle (NP) folate-receptor-targeted laser-activatable poly(lactide-co-glycolic acid) (PLGA) NPs loaded with paclitaxel (Ptx)/indo-cyanine green (ICG)-folic acid-polyethylene glycol (PEG)-PLGA-Ptx@ICG-perfluorohexane (Pfh)- using safe and approved materials and drugs, which would facilitate clinical translation. With laser irradiation, highly efficient photothermal therapy can be achieved. Additionally, targeted NPs can be activated by near-infrared laser irradiation at a specific region, which leads to the sharp release of Ptx at areas of high folate-receptor expression and ensures a higher Ptx concentration within the tumor region, thereby leading to chemo/photothermal synergistic antitumor efficacy. Meanwhile, the NPs can be used as a dual-modality contrast agent for photoacoustic and ultrasound imaging.Materials and methodsFA-PEG-PLGA-Ptx@ICG-Pfh NPs were prepared by sonification method and characterized for physicochemical properties. Cytotoxicity and in vivo biocompatibility were evaluated respectively by CCK8 assay and blood analysis. NPs as dual-modality contrast agents were evaluated by photoacoustic/ultrasound imaging system in vitro and in vivo. In vitro anticancer effect and in vivo anticancer therapy was evaluated by CCK8 assay and MDA-MB231 tumor-bearing mice model.ResultsFA-PEG-PLGA-Ptx@ICG-Pfh NPs were in the size of 308±5.82 nm with negative zeta potential and showed excellent photothermal effect. The NPs could be triggered sharp release of Ptx by laser irradiation, and showed the good biocompatibility in vitro and in vivo. Through photoacoustic/ultrasound imaging, the NPs showed an excellent ability as dual-modality contrast agents in vitro and in vivo. FA-PEG-PLGA-Ptx@ICG-Pfh NPs with laser irradiation showed the best anticancer efficacy in vitro and in vivo.ConclusionSuch a biocompatible and novel theranostic NP is expected to integrate dual-modality imaging with improved therapeutic efficacy and provide a promising paradigm for cancer therapy.

The past, present, and future of breast cancer models for nanomedicine development

“…The authors reported enhanced tumor accumulation and antitumor efficacy following the added use of a pH-responsive peptide (H7K(R 2 ) 2 ) to target the TME. In another example, Liu et al evaluated the antitumor efficacy of a folate-receptor-targeted laser-activable poly(lactide-co-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green in subcutaneous MDA-MB-231-derived tumors in BALB/c nude mice [193] . Laser-mediated activation permitted the controlled release of paclitaxel in areas of high folate-receptor densities, which demonstrated high antitumor efficacy.…”

State-of-the-Art Preclinical Photoacoustic Imaging in Oncology: Recent Advances in Cancer Theranostics

“…The authors hypothesized future developments for the MSNPs system such as preclinical assessment of tumor response to the gemcitabine or other chemotherapeutics, and their potential use for improving clinical staging of pancreatic cancer combined with simultaneous treatment. More recently, Liu and colleagues [44] employed a similar targeting strategy in xenograft mouse models of breast cancer for theranostic purposes. They developed folate-receptor-targeted (FA) laser-activatable poly(lactide-co-glycolic acid) (PLGA) NPs loaded with ICG and paclitaxel (Ptx) in order to combine effectively PTT and drug delivery.…”

“…These NPs were successfully applied in vivo as contrast agent for dual US-PAI in mice-bearing breast cancer. Furthermore, FA-PLGA-ICG-Ptx NPs showed the capability to selectively damage cancer cells both by the photothermal effect and by Ptx release after laser irradiation, significantly reducing the growth of tumors with high FR expression [44].…”

<p>G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma</p>

“…There have been many studies on nanobubbles as drug carriers, but low drug loading efficiency is still a common problem. The drug loading efficiency of some hydrophobic drugs, such as paclitaxel (PTX) and doxorubicin (DOX), was ranged from 2.666 ± 0.092% to 6.69 ± 0.69% in the literature, [21][22][23][24][25] and the drug loading efficiency of G250-TNBs in this study was 5.23% ± 0.91%. On the one hand, the low efficiency of drug loading may be due to the fact that the nanobubbles are vesicles with the perfluoropropane gas wrapped in the lipid envelope, and TEM is a hydrophobic drug that encapsulates only in the lipid envelope.…”