Multifunctional Nanoparticle Loaded Injectable Thermoresponsive Hydrogel as NIR Controlled Release Platform for Local Photothermal Immunotherapy to Prevent Breast Cancer Postoperative Recurrence and Metastases

Abstract

For breast cancer patients who have undergone breast‐conserving surgery, effective treatments to prevent local recurrences and metastases is very essential. Here, a local injectable therapeutic platform based on a thermosensitive PLEL hydrogel with near‐infrared (NIR)‐stimulated drug release is developed to achieve synergistic photothermal immunotherapy for prevention of breast cancer postoperative relapse. Self‐assembled multifunctional nanoparticles (RIC NPs) are composed of three therapeutic components including indocyanine green, a photothermal agent; resiquimod (R848), a TLR‐7/8 agonist; and CPG ODNs, a TLR‐9 agonist. RIC NPs are physically incorporated into the thermosensitive PLEL hydrogel. The RIC NPs encapsulated PLEL hydrogel (RIC NPs@PLEL) is then locally injected into the tumor resection cavity for local photothermal therapy to ablate residue tumor tissues and produce tumor‐associated antigens. At the same time, NIR also triggers the release of immune components CPG ODNs and R848 from thermoresponsive hydrogels PLEL. The released immune components, together with tumor‐associated antigens, work as an in situ cancer vaccine for postsurgical immunotherapy by inducing effective and sustained antitumor immune effect. Overall, this work suggests that photothermal immunotherapy based on local hydrogel delivery system has great potential as a promising tool for the postsurgical management of breast cancer to prevent recurrences and metastases.

Novel zwitterionic vectors: Multi-functional delivery systems for therapeutic genes and drugs

“…Thermo-responsiveness is one of the most widely used stimulus that can lead to reversible phase transition with just a slight change of temperature, so that thermo-sensitive DDSs have attracted much attention to control drug release [123] . As mentioned in the classification chapter, SB-based polymers such as PSBMA exhibit a sharp phase transition below their UCST in aqueous solution owning to the strong electrostatic interactions among their SB moieties [124] .…”

Injectable hydrogels of newly designed brush biopolymers as sustained drug-delivery vehicle for melanoma treatment

“…14 Porous polymeric hydrogels have been used extensively as carriers for sustained/slow drug release, where the rate of release is controlled through diffusion process or by the combination of diffusion and erosion of the matrix. [15][16][17] Recently, the use of natural polymers over synthetic polymers has attained a significant importance for drug-delivery applications, because of their biodegradability, cost effectiveness, and non-toxicity. However, there are some limitations with natural polymers like uncontrolled hydration rate, microbial contamination, and viscosity drop during storage.…”

Recent Advances in Hyperthermia Therapy‐Based Synergistic Immunotherapy

“…[66] Wei et al fabricated a self-assembled nanoplatform by coloading immunoadjuvants of CpG, resiquimoid (R848), and a photothermal agent, indocyanine green (ICG), into the thermosensitive PLEL hydrogel, which elicited photothermal enhanced immune responses against postsurgical recurrence and metastasis of breast cancer. [67] Some other immunoadjuvants, including R837, aluminum hydroxide, ovalbumin (OVA), and glycated chitosan, have also been combined with HTT to achieve a synergistic enhanced therapeutic effect. [68,69] Despite the tremendous improvement of commercial immunoadjuvants, insufficient intracellular transport and inevitable systemic toxicity have remained a challenge.…”