Abstract
Smart hydrogels that undergo structural changes in response to stimuli (for example, pH, heat, light) have promising biomedical applications as delivery systems, especially for the locally controlled release of drugs. Early prevention of locoregional recurrence (LRR) is critical for patients who have undergone breast-conserving therapy. This work reports the preparation of a hybrid hydrogel system in which gold nanorods (GNRs) were doped into a thermally responsive hydrogel. A near-infrared (NIR) laser was used to trigger the release of loaded Doxorubicin (DOX) by utilizing the photothermal effect of GNRs to induce the contraction of the thermo-responsive hydrogels. In a 4T1 breast cancer model of the in vivo locoregional prevention of post-operative recurrence, we found that after NIR irradiation, DOX/GNR-embedded Methoxylpoly(ethylene glycol)-poly(ɛ-caprolactone)-acryloyl chloride (PECA)/glycidylmethacrylated chitooligosaccharide (COS-GMA)/N-isopropylacrylamide (NIPAm)/acrylamide (AAm) (PCNA) hydrogels (DOX-PCNA-GNR hydrogels) significantly reduced tumor recurrence to 16.7%, compared with 50% for DOX-PCNA-GNRs without NIR irradiation, 83.3% for PCNA-GNRs with NIR irradiation, 100% for PCNA-GNRs without NIR irradiation, 83.3% for single systemic or local administration of Dox, 100% for intravenous DOX administration once or three times, and 100% for the blank control. This study demonstrates that these DOX-PCNA-GNR hybrid hydrogels with NIR-triggered thermo-responsive drug release exhibit great potential in preventing post-operation cancer relapse. A thermoresponsive hydrogel containing gold nanorods can reduce breast cancer recurrence by delivering thermotherapeutic and chemotherapeutic drug. Effective inhibition of breast cancer relapse remains an important challenge. Now, Zhi Yong Qian and co-workers at the State Key Laboratory of Biotherapy and Cancer Center and Tsinghua University in China have demonstrated that the combination of photothermal therapy and chemotherapy considerably inhibits the postoperative relapse of breast cancer. They synthesized the hydrogel by heat-initiated free-radical polymerization. The researchers found that applying near-infrared radiation simultaneously heated the gold nanorods and caused the thermoresponsive hydrogel to contract; this ‘squeezing’ of the hydrogel caused it to release the chemotherapy drug faster. This combined approach has the advantage of reducing systemic toxicity since it limits non-selective application of the drug. We prepared a hybrid hydrogel system by doping the gold nanorods (GNRs) into the thermal responsive hydrogel. The near-infrared (NIR) laser was used to trigger the release of loaded Doxorubicin (DOX) by utilizing the photothermal effect of GNRs to induce the contraction of thermo-responsive hydrogels. The development of the hydrogel as the carrier is for the chemo-photothermal co-therapy of local breast cancer recurrence. The DOX-PCNA-GNRs hydrogel effectively prevented breast cancer recurrence after primary tumor resection in a mouse model.
Highlights
Breast cancer is associated with a very high mortality[1,2,3] and has profound implications for women’s health.[4,5] Various technologies have been proposed for breast cancer therapy, including surgical removal, site-specific radiotherapy or both
Synthesis and characterization of gold nanorods (GNRs)-loaded hydrogels The GNR-loaded hydrogel (Scheme 1) was composed of GNRs and PCNA hydrogel copolymerized with methoxylpoly(ethylene glycol)-poly(ε-caprolactone)-acryloyl chloride (PECA) (Supplementary Figure S1 in the Supplementary Information), glycidylmethacrylated chitooligosaccharide (COS-glycidyl methacrylate (GMA)) (Supplementary Figure S2 in the Supplementary Information), NIPAm and AAm
The absorption band at ~ 1620 cm − 1 is attributed to the C = C stretching vibration and can be clearly observed in the PECA and COS-GMA FTIR spectra
Summary
Breast cancer is associated with a very high mortality[1,2,3] and has profound implications for women’s health.[4,5] Various technologies have been proposed for breast cancer therapy, including surgical removal, site-specific radiotherapy or both. This study demonstrates that these DOX-PCNA-GNR hybrid hydrogels with NIR-triggered thermo-responsive drug release exhibit great potential in preventing post-operation cancer relapse. Photothermal effects of PCNA-GNR hydrogels The hydrogel was irradiated from the right side with an 808-nm laser at a power density of 2.5 W cm − 2 for 5 min, and the temperature was recorded by a Fluke TI32 Infrared (IR) thermal camera (Infrared Cameras, Fluke, Avery, WA, USA) until the sample reached room temperature.
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