A biodegradable thermo-responsive hybrid hydrogel: therapeutic applications in preventing the post-operative recurrence of breast cancer

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(ε-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-PCNAGNRs 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.

Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances

“…This mechanism increases the efficiency of drug release at the cancer site in addition to hyperthermia of the cancerous cells. Ying Qu et al 293 developed a combined hydrogel system by doping gold nanorods (GNRs), as the photothermal agents, into the DOX embedded hydrogels. They demonstrated that efficient release of DOX from hydrogel matrix, by means of stimulating GNRs photothermal agents, resulted in a remarkable decrease of the tumor recurrence in mice 4T1 breast cancer models.…”

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

“…29 For example, gold nanorods doped into a thermally responsive hydrogel made with methoxylpoly(ethylene glycol)-poly(ε-caprolactone)-acryloyl chloride, glycidylmethacrylated chitooligosaccharide, N -isopropylacrylamide, and acrylamide, were able to induce the contraction of the thermo-responsive hydrogels and trigger the release of loaded doxorubicin to inhibit breast cancer under NIR irradiation (Figure 3). 73 Other NIR-absorbing nanoparticles such as carbon nanotubes 113 and graphene oxide nanoparticles 116 were also incorporated into thermo-responsive polymers to harness NIR for remotely controlled drug delivery. Recently, upconversion core-shell nanoparticles made from NaYF 4 :TmYb (core = NaYF 4 :0.5 mol % Tm 3+ :30 mol % Yb 3+ ; shell = NaYF 4 , in a uniform hexagonal prism shape with an average length of 36.0 ± 1.1 nm and width of 32.0 ± 1.5 nm) capable of converting NIR light into UV light were also integrated with a photo-responsive hydrogel consisting of acrylamide monomer and the photocleavable PEG cross-linker.…”

Carbohydrate polymer based pH-sensitive IPN microgels: Synthesis, characterization and drug release characteristics

“…Over the past decades, different polymeric therapeutics have begun to make a vital contribution for tumor targeting in cancer therapy. In cancer drug delivery, different polymer based hydrogels have been designed and demonstrated as drug carrier systems [4] [5] [6,7] [8]. Among the several polymeric systems developed, systems containing biodegradable polymers have been used for localized drug delivery to control therapeutic drug level over a period of months, since the degradation of polymer is slow [9].…”