New medical devices with anti-inflammatory properties are critical to prevent inflammatory processes and infections in medical/surgical procedures. In this work, we present a novel functionalization of silicone for medical use with a polymeric prodrug and a thermosensitive polymer, by graft polymerization (gamma rays), for the localized release of salicylic acid, an analgesic, and anti-inflammatory drug. Silicone rubber (SR) films were functionalized in two stages using graft polymerization from ionizing radiation (⁶⁰Co). The first stage was grafting poly(N-vinylcaprolactam) (PNVCL), a thermo-sensitive polymer, onto SR to obtain SR-g-PNVCL. In the second stage, poly(2-methacryloyloxy-benzoic acid) (P2MBA), a polymeric prodrug, was grafted to obtain (SR-g-PNVCL)-g-P2MBA. The degree of functionalization depended on the concentrations of monomers and the irradiation dose. The films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy/energy-dispersive X-ray spectrometry (SEM–EDX), thermogravimetric analysis (TGA), and contact angle. An upper critical solution temperature (UCST) of the films was demonstrated by the swelling degree as a temperature function. (SR-g-PNVCL)-g-P2MBA films demonstrated hydrolysis-mediated drug release from the polymeric prodrug, pH, and temperature sensitivity. GC–MS confirmed the presence of the drug (salicylic acid), after polymer hydrolysis. The concentration of the drug in the release media was quantified by HPLC. Cytocompatibility and thermo-/pH sensitivity of functionalized medical silicone were demonstrated in cancer and non-cancer cells.

Silicone rubber (SR) is a material used for medical procedures, with a common example of its application being in implants for cosmetic or plastic surgeries. It is also an essential component for the development of medical devices. SR was functionalized with the polymeric prodrug of poly(2-methacryloyloxy-benzoic acid) (poly(2MBA)) to render the analgesic anti-inflammatory drug salicylic acid by hydrolysis. The system was designed by functionalizing SR films (0.5 cm × 1 cm) with a direct grafting method, using gamma irradiation (⁶⁰Co source) to induce the polymerization process. The absorbed dose (from 20 to 100 kGy) and the monomer concentration (between 0.4 and 1.5 M) were critical in controlling the surface and the bulk modifications of SR. Grafting poly(2MBA) onto SR (SR-g-2MBA) were characterized by attenuated total reflectance Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy/energy-dispersive X-ray spectrometry, fluorescence microscopy, the contact angle, and the swelling. SR-g-2MBA demonstrated the drug’s sustained and pH-dependent release in simulated physiological mediums (pH = 5.5 and 7.4). The drug’s release was quantified by high-performance liquid chromatography and confirmed by gas chromatography–mass spectrometry. Finally, cytocompatibility was demonstrated in murine fibroblast and human cervical cancer cell lines. The developed systems provide new polymeric drug release systems for medical silicone applications.

The spontaneous interaction between human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) and non-functionalized gold nanoparticles (nfGNPs) interferes with the nfGNPs’ salt-induced aggregation, inhibiting the red–blue color shift in the presence of NaCl. Electron microscopy and competition studies showed that color-shift inhibition is a consequence of direct nfGNP–VLP interaction and, thus, may produce a negative impact on the virus entry cell process. Here, an in vitro infection system based on the HPV16 pseudovirus (PsV) was used to stimulate the natural infection process in vitro. PsVs carry a pseudogenome with a reporter gene, resulting in a fluorescent signal when PsVs infect a cell, allowing quantification of the viral infection process. Aggregation assays showed that nfGNP-treated PsVs also inhibit color shift in the presence of NaCl. High-resolution microscopy confirmed nfGNP–PsV complex formation. In addition, PsVs can interact with silver nanoparticles, suggesting a generalized interaction of metallic nanoparticles with HPV16 capsids. The treatment of PsVs with nfGNPs produced viral infection inhibition at a higher level than heparin, the canonical inhibitor of HPV infection. Thus, nfGNPs can efficiently interfere with the HPV16 cell entry process and may represent a potential active component in prophylactic formulations to reduce the risk of HPV infection.

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that negatively regulate gene expression. MiRNAs regulate fundamental biological processes and have significant roles in several pathologies, including cancer. Cervical cancer is the best-known example of a widespread human malignancy with a demonstrated viral etiology. Infection with high-risk human papillomavirus (hrHPV) has been shown to be a causative factor for cervical carcinogenesis. Despite the occurrence of prophylactic vaccines, highly sensitive HPV diagnostics, and innovative new therapies, cervical cancer remains a main cause of death in developing countries. The relationship between hrHPV infection and cervical cancer depends on the integration of viral DNA to the host genome, disrupting the viral regulator E2 and the continuous production of the viral E6 and E7 proteins, which are necessary to acquire and maintain a transformed phenotype but insufficient for malignant cervical carcinogenesis. Lately, miRNAs, the tumor microenvironment, and immune evasion have been found to be major players in cervical carcinogenesis after hrHPV infection. Many miRNAs have been widely reported as deregulated in cervical cancer. Here, the relevance of miRNA in HPV-mediated transformation is critically reviewed in the context of the natural history of hrHPV infection and cervical cancer.

This study aims to design microgels that are thermo- and pH-sensitive for controlled doxorubicin (Dox) release in response to tumor microenvironment changes. N-isopropylacrylamide (NIPAAm) is widely used for thermoresponsive tumor-targeted drug delivery systems for the release of therapeutic payloads in response to temperature changes. Herein, a NIPAAm microgel (MP) that is responsive to temperature and pH was designed for the smart delivery of Dox. MP was made from NIPAAm, and polyethylene glycol methyl ether methacrylate (PEGMA) was copolymerized with 5%, 10%, or 15% mol of methacryloylamido hexanoic acid, (CAM5) an amphiphilic acid. We characterized the microgels using FTIR-ATR, DLS, and FESEM. The MP 10% CAM5 exhibited a particle size of 268 nm, with a transition temperature of 44 °C. MP had a drug loading capacity of 13% and entrapment efficiency of 87%. Nearly 100% of the Dox was released at pH 5 and 42 °C, compared to 30% at pH 7.4 and 37 °C. MP 10% CAM5 showed cytocompatibility in HeLa cells using the MTT assay. However, the cell viability assay showed that dox-MP was twice as effective as free Dox. Specifically, 3 μg/mL of free Dox resulted in 74% cell viability, while the same doses of Dox in NP reduced it to 35%. These results are promising for the future tumor-targeted delivery of antineoplastic-drugs, as they may reduce the side effects of Dox.