Photothermal hydrogel platform for prevention of post-surgical tumor recurrence and improving breast reconstruction

Abstract

Background: As one of the leading threats for health among women worldwide, breast cancer has high morbidity and mortality. Surgical resection is the major clinical intervention for primary breast tumor, nevertheless high local recurrence risk and breast tissue defect remain two main clinical dilemmas, seriously affecting survival and quality of life of patients.

Experimental: We developed a thermoresponsive and injectable hybrid hydrogel platform (IR820/Mgel) by integration of co-loaded porous microspheres (MPs) and IR820 for preventing postoperative recurrence of breast cancer via photothermal therapy and promoting subsequent breast reconstruction.

Results: Our results suggested that IR820/Mgel could quickly heated to more than 50.0 ℃ under NIR irradiation, enabling killing effect on 4T1 cells in vitro and prevention effect on post-surgical tumor recurrence in vivo. In addition, the hydrogel platform was promising for its minimal invasion and capability of filling irregularly shaped defects after surgery, and the encapsulated MPs could help to increase the strength of gel to realize a long-term in situ function in vivo, and promoted the attachment and anchorage property of normal breast cells and adipose stem cells.

Conclusions: This photothermal hydrogel platform provides a practice paradigm for preventing locally recurrence of breast cancer and a potential option for reconstruction of breast defects.

Keywords: Breast cancer; Breast reconstruction; Hydrogel; Microspheres; Photothermal therapy.

Scheme 1

The scheme of hydrogel platform (IR820/Mgel) preparation and its applications for preventing post-surgical tumor recurrence and improving breast reconstruction. The IR820/Mgel helps forward IR820, as a photothermal agent retention in tumor site, thus presents an excellent photothemal performance for preventing locally recurrence of cancer. In addition, the hydrogel platform as a filler could repair the breast defects, at the same time porous MPs offer a well support for cells attachment and anchorage, which may provide benefits for breast reconstruction

Fig. 1

SEM micrographs of PLGA MPs (A, B), gel (C, D), and Mgel (E, F)

Fig. 2

The rheological properties and in vitro photothermal properties of hydrogel platform. A The thermoresponsive behavior of gel and Mgel. B The sol–gel phase transition time of gel and Mgel. C IR thermographic images of Mgel with different concentrations of IR820 after exposure to an 808 nm laser at a power density of 1 W/cm². D The temperature–time profile of IR820/Mgel with different concentrations of IR820

Fig. 3

In vitro photothermal effect of hydrogel platform. A The images of live and dead 4T1 cells stained by calcein-AM/PI (green signal, live cells; red signal, dead cells) with various treatments. The concentration of IR820 was 100 µg/mL, and the laser power density was 1 W/cm² (808 nm, 5 min). B Calculated liveratios of 4T1 cells with various treatments. P < 0.01 (**), and P < 0.001 (***)

Fig. 4

In vitro and in vivo biocompatibility of hydrogel platform. A Effect of hydrogel extracts on cell viability measured by MTT assay. B Histological observation of biocompatibility assay at different time points

Fig. 5

The retention effect of hydrogel platform. In vivo distribution and retention profile of IR820/gel via intravital fluorescence imaging

Fig. 6

The surgical procedure. A Tumor resection and hydrogel platform injection procedure. a Surgery was performed; b Mimicked incomplete tumor removal; c The hydrogel platform was injected into the tumor cavity;d The wound was closed. Strategies to control resected tumor size: B Tumor volume was accurately recorded before surgery, and mice with similar tumor volume were selected for randomly grouping; C A single experimenter performed the surgery to remove about 90% of the tumor volume; D Resected tumors were weighed and photographed to ensure the size of the residual tumors in each group are relatively uniform

Fig. 7

In vivo photothermal activities in a tumor-bearing model and anti-tumor efficacy of the hydrogel platform mediated photothermal therapy. A The dynamic photothermal images and B temperature–time profile at the tumor site under NIR irradiation (808 nm, 1 W/cm², 5 min). C Tumor growth curves and D body weight of mice following various treatments. E Excised tumors image at day 14 after surgery and administration. G1, Control; G2, IR820/Mgel; G3, L; G4, Free IR820+L; G5, IR820/Mgel+L. P value < 0.001 (***)

Fig. 8

Histological analysis of the tumor tissues and major organs. A Ki67 immunohistochemical staining and representative mean Ki67 LI in each group; B H&E staining of major organs of tumor-bearing mice receiving different treatments. G1, Control; G2, IR820/Mgel; G3, L; G4, Free IR820+L; G5, IR820/Mgel+L. P value < 0.001 (***)

Fig. 9

In vitro and in vivo breast construction property of hydrogel platform. A–D SEM micrographs of MCF-10A cells adhered MPs. E, F In vivo shaping and morphology change of the gel