Abstract
The combination of chemotherapy and phototherapy has attracted increasing attention for cancer treatment in recent years. In the current study, porous PdPt bimetallic nanoparticles (NPs) were synthesized and used as delivery carriers for the anti-cancer drug doxorubicin (DOX). DOX@PdPt NPs were modified with thiol functionalized hyaluronic acid (HA-SH) to generate DOX@PdPt@HA NPs with an average size of 105.2 ± 6.7 nm. Characterization and in vivo and in vitro assessment of anti-tumor effects of DOX@PdPt@HA NPs were further performed. The prepared DOX@PdPt@HA NPs presented a high photothermal conversion efficiency of 49.1% under the irradiation of a single 808 nm near-infrared (NIR) laser. Moreover, NIR laser irradiation-induced photothermal effect triggered the release of DOX from DOX@PdPt@HA NPs. The combined chemo-photothermal treatment of NIR-irradiated DOX@PdPt@HA NPs exerted a stronger inhibitory effect on cell viability than that of DOX or NIR-irradiated PdPt@HA NPs in mouse mammary carcinoma 4T1 cells in vitro. Further, the in vivo combination therapy, which used NIR-irradiated DOX@PdPt@HA NPs in a mouse tumor model established by subcutaneous inoculation of 4T1 cells, was demonstrated to achieve a remarkable tumor-growth inhibition in comparison with chemotherapy or photothermal therapy alone. Results of immunohistochemical staining for caspase-3 and Ki-67 indicated the increased apoptosis and decreased proliferation of tumor cells contributed to the anti-tumor effect of chemo-photothermal treatment. In addition, DOX@PdPt@HA NPs induced negligible toxicity in vivo. Hence, the developed nanoplatform demonstrates great potential for applications in photothermal therapy, drug delivery and controlled release.
Highlights
Chemotherapy has contributed greatly to reduce cancer mortality but usually accompanies serious side effects and lacks specificity toward tumor cells [1,2]
The photothermal conversion efficiency of PdPt, PdPt@Hyaluronic acid (HA) and DOX@PdPt@HA NPs was further calculated to be 48.6%, 49.8% and 49.1%, respectively (DSuOpXp@lePmdPent@taHryAMNaPtserwiaelrse, FwigeullrdeisSp3e).rsTehdeivnaaluneasqaureeohuisgshoelruttihoannwthitaht PofDtIhveaAluuesnoanf 0o.r1o3d6s±(204.0%1)7aanndd C0u.1S43N±Ps0.(03112.1, %re)s,pwechtiicvhelayr.e widely used for Photothermal therapy (PTT) [36]
The results indicated the upregulation of apoptosis and downregulation of proliferation contributed to the enhanced therapeutic efficacy of chemo-phototherapy of DOX@PdPt@HA NPs in comparison with chemotherapy or PTT alone
Summary
Chemotherapy has contributed greatly to reduce cancer mortality but usually accompanies serious side effects and lacks specificity toward tumor cells [1,2]. The combination of chemotherapy and phototherapy, which could be delivered by nanoscale carriers for precise drug delivery, was considered an attractive approach to reducing side effects and enhancing therapeutic efficacy in cancer treatment in recent years [3,4,5]. Photothermal therapy (PTT) is one of the primary types of phototherapy methods that employs the heat generated from the absorbed optical energy by photothermal agents to ablate tumor cells [6,7]. To realize combined chemo-photothermal therapy, anti-cancer drugs were loaded into the nanoparticles (NPs) containing photothermal agents [13,14]. The strategies to prepare NPs with both photothermal property and drug-loading capacity are anticipated for the advantages of simplifying the synthesis process [15]
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