An injectable thermosensitive hydrogel loaded with a theranostic nanoprobe for synergistic chemo-photothermal therapy for multidrug-resistant hepatocellular carcinoma.
Shanzhou HuangZuyi MaChengjun SunQi ZhouZhenchong LiShujie WangQian YanChunsheng LiuBaohua HouChuanzhao ZhangPublished in: Journal of materials chemistry. B (2022)
Multi-drug resistance (MDR) is a complicated cellular defense mechanism for tumor cells to resist chemotherapy drugs, which is also the main cause of chemotherapy failure. In this study, a local injectable hydrogel delivery system was used to construct an on-demand sustained-release platform with the advantages of chemotherapy, photothermal therapy (PTT), and magnetic resonance imaging (MRI). It could achieve synergistic chemo-photothermal therapy and real-time evaluation of the therapeutic effects ( via MRI) for MDR hepatocellular carcinoma (HCC). Furthermore, after a single administration, the prepared hydrogel with a theranostic nanoprobe could release the therapeutic agents on demand for up to 14 d. Firstly, doxorubicin (DOX) and gold-manganese oxide (Au-MnO) nanoparticles (NPs) were incorporated into liposome-based self-assembled micelles, then loaded into the thermosensitive hydrogel (F127) to form DOX@Au-MnO-L NPs/F127 hydrogel (DAML/H). The prepared NP complex showed a spherical morphology with a narrow size distribution. The prepared hydrogel drug delivery system had injectable properties and stable photothermal conversion. Both the DOX@Au-MnO-L NPs and DAML/H showed controlled drug release under near infrared (NIR) laser irradiation. The in vitro MRI studies indicated that the prepared DAML/H had a high relaxation rate (14.38 mM -1 s -1 ) and good MRI scanning sensitivity conditions. The in vitro and in vivo results suggested the synergistic chemo-photothermal therapy of DAML/H with NIR irradiation (808 nm, 1 W cm -2 , 10 min) improved the antitumor efficacy for MDR HCC. The in vivo retention experiment of Au in tumors indicated that the prepared hydrogel drug delivery system (DAML/H) had a good ability to retain Au in the tumor for a long time (at least 14 d). The western blotting results revealed that DAML/H with laser treatment could effectively downregulate P-glycoprotein (P-gp), p53 and antiapoptotic protein (Bcl-2), whereas the expression level of proapoptotic protein (Bax) and caspase-3 were increased. Therefore, DAML/H could serve as a promising synergistic chemo-photothermal therapy for MDR HCC, and a single administration might achieve long-term (14 d), on-demand, sustained-release treatment of tumors.
Keyphrases
- drug delivery
- cancer therapy
- drug release
- multidrug resistant
- photodynamic therapy
- magnetic resonance imaging
- hyaluronic acid
- contrast enhanced
- sensitive detection
- locally advanced
- tissue engineering
- reduced graphene oxide
- drug resistant
- gram negative
- acinetobacter baumannii
- diffusion weighted imaging
- fluorescence imaging
- computed tomography
- high resolution
- high throughput
- klebsiella pneumoniae
- small molecule
- oxidative stress
- magnetic resonance
- replacement therapy
- living cells
- fluorescent probe
- induced apoptosis
- gold nanoparticles
- endoplasmic reticulum stress
- binding protein
- cell death
- amino acid
- squamous cell carcinoma
- oxide nanoparticles
- single molecule
- escherichia coli
- quantum dots
- radiation induced
- drug induced
- long non coding rna