Biomedical Materials

Current development of theragnostic nanoparticles for women’s cancer treatment

Abstract In the biomedical industry, nanoparticles (NPs—exclusively small particles with size ranging from 1–100 nanometres) are recently employed as powerful tools due to their huge potential in sophisticated and enhanced cancer theragnostic (i.e. therapeutics and diagnostics). Cancer is a life-threatening disease caused by carcinogenic agents and mutation in cells, leading to uncontrolled cell growth and harming the body’s normal functioning while affecting several factors like low levels of reactive oxygen species, hyperactive antiapoptotic mRNA expression, reduced proapoptotic mRNA expression, damaged DNA repair, and so on. NPs are extensively used in early cancer diagnosis and are functionalized to target receptors overexpressing cancer cells for effective cancer treatment. This review focuses explicitly on how NPs alone and combined with imaging techniques and advanced treatment techniques have been researched against ‘women’s cancer’ such as breast, ovarian, and cervical cancer which are substantially occurring in women. NPs, in combination with numerous imaging techniques (like PET, SPECT, MRI, etc) have been widely explored for cancer imaging and understanding tumor characteristics. Moreover, NPs in combination with various advanced cancer therapeutics (like magnetic hyperthermia, pH responsiveness, photothermal therapy, etc), have been stated to be more targeted and effective therapeutic strategies with negligible side effects. Furthermore, this review will further help to improve treatment outcomes and patient quality of life based on the theragnostic application-based studies of NPs in women’s cancer treatment.

Design, modeling and 3D printing of a personalized cervix tissue implant with protein release function

Abstract Cervical cancer induced by human papillomavirus (HPV) causes severe morbidity worldwide. Although cervical conization has been widely accepted as the most conventional surgery against cervical cancer, tissue defects and high recurrence rates have a significant negative impact on women’s mental and physical health. Herein we developed an implantable, personalized cervical implant with drug release function using 3D printing technology. The cervical implant was designed in cone-shape with hieratical porous structures according to the clinical data, 3D-printed using polyurethane by low-temperature deposition manufacturing (LDM), and finished by lyophilization. Anti-HPV protein was loaded into the porous structure under negative pressure afterwards. Elastic biomedical polyurethane and the porous structure ensured that these cervical implants were equipped with tailored mechanical properties comparable to physiological cervix tissue. Cytotoxicity and cytocompatibility tests indicated that these 3D-printed cervical implants supported cell adhesion and growth. More importantly, the cervical implants with regulated pores could help to quantitatively control the loading and release of anti-HPV protein to inhibit dissociative viruses near the cervix validly. As a result, the 3D-printed cervical implants in the present study showed considerable potential for use as functional tissue implants against HPV infection after cervical conization.

Folic acid–encapsulated silver nitroprusside nanoparticles for targeted therapy in ovarian cancer

Abstract Ovarian cancer is the most prevalent fatal, gynecological malignancy in women, resulting in poor survival rate (fifth in cancer deaths) due to its asymptomatic nature. Unmet medical challenges for ovarian cancer are associated with several constraints such as poor bioavailability, nonspecificity, and toxicity-related issues. Targeted drug delivery systems may overcome the existing limitations. Utilizing the concept of overexpression of folate receptors (FRs) in ovarian carcinoma, we have designed FRs-targeted drug delivery systems (AgNNPs-FA) by combining silver nitroprusside nanoparticles (AgNNPs) because of their inherent anticancer properties, as established by our group, and folic acid (FA) as targeting agent that attack FRs in this study. Initially, both AgNNPs and AgNNPs–FA were designed and later characterized using several analytical tools such as dynamic light scattering, x-ray diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, high-performance liquid chromatography, and Fourier transform–infrared spectroscopy, etc. The in vitro cell viability assay in a Chinese hamster ovary cell line suggests the biocompatible nature of AgNNPs–FA. The targeted anticancer activity of the AgNNPs–FA is established in human ovarian adenocarcinoma (SK-OV-3) via several in vitro assays and compared with AgNNPs. All in vitro assays (cell viability assay, thymidine incorporation assay, scratch assay, cell cycle, apoptosis assay, and tunnel assay) in SK-OV-3 and in vivo experiments (chorioallantoic membrane assay) in fertilized eggs with AgNNPs–FA exhibit more anticancer activity in a targeted fashion than AgNNPs. The plausible mechanisms behind the anticancer activity of the nanoparticles were demonstrated using the ROS assay (DCFDA and DHE staining), JC-1 staining, immunocytochemistry staining (Ki-67), and Western blot analysis. The results altogether support the idea that this targeted drug delivery system could be used as an alternative treatment strategy for ovarian cancer and other cancers with the overexpression of FRs.

Multifunctional targeting of docetaxel plus bakuchiol micelles in the treatment of invasion and metastasis of ovarian cancer

Abstract The invasion and metastasis of tumors pose significant challenges in the treatment of ovarian cancer (OC), making it difficult to cure. One potential treatment approach that has gained attention is the use of matrix metalloproteinase reactive controlled release micelle preparations. In this study, we developed a novel PEG5000-PVGLIG-hyaluronic acid docetaxel/bakuchiol (PP-HA-DTX/BAK) micelles formulation with desirable characteristics such as particle size, narrow polydispersity index, and a ZETA potential of approximately −5 mV. The surface modification with HA facilitates tumor penetration into the tumor interior, while the incorporation of DSPE-PEG2000-PVGLIG-PEG5000 helps conceal DSPE-PEG2000-HA, reducing off-target effects and prolonging drug circulation time in vivo. Both in vitro and in vivo experiments demonstrated that these micelles effectively inhibit proliferation, invasion, and metastasis of OC cells while promoting apoptosis. Therefore, our findings suggest that PP-HA-DTX/BAK micelles represent a safe and effective therapeutic strategy for treating OC.

Non-interference delivery of Ce6 and DOX in NIR light-responsive liposomes for synergetic cervical cancer therapy

Abstract Multi-model combination treatment of malignant tumors can make up for the shortcomings of single treatment through multi-target and multi-path to achieve more ideal tumor treatment effect. However, the mutual interference of different drugs in the delivery process in vivo and the difficulty of effective drug accumulation in tumor cells are the bottlenecks of combined therapy. To this project, light-responsive liposomes loading doxorubicin (DOX) and chlorin e6 (Ce6) (DOX-Ce6-Lip) without mutual interference were engineered by thin film hydration method. This kind of nano-drug delivery system increased the drugs concentration accumulated in tumor sites through enhanced permeability and retention effect, and reduced the toxic and side effects of drugs on normal tissues in vivo. In addition, after entering the tumor cells, Ce6 produced a large number of reactive oxygen species under 660 nm NIR laser irradiation, which further oxidized the unsaturated fatty acid chain in the liposomes and caused the collapse of the liposomes, thus realizing the stimulus-responsive release of Ce6 and DOX. The concentrations of DOX and Ce6 in the tumor cells rapidly reached the peak and achieved a more effective combination of chemotherapy and photodynamic therapy (PDT). Consequently, DOX-Ce6-Lip followed by 660 nm NIR irradiation achieved an efficient tumor growth inhibition of 71.90 ± 3.14%, indicating the versatile potential of chemotherapy and PDT. In conclusion, this study provides a delivery scheme for drugs with different solubilities and an effectively combined anti-tumor therapy method.

Double-layer hollow mesoporous silica nanoparticles for ultrasound-guided photodynamic treatment

Abstract Cervical carcinoma persists as a major global public health burden. While conventional therapeutic modalities inevitably cause ablation of adjacent non-tumorous tissues, photodynamic therapy (PDT) offers a targeted cytotoxic strategy through a photosensitizing agent (PS). However, the hydrophobicity and lack of selective accumulation of promising PS compounds such as zinc(II) phthalocyanine (ZnPc) impedes their clinical translation as standalone agents. The present study sought to incorporate ZnPc within double-layer hollow mesoporous silica nanoparticles (DHMSN) as nanocarriers to enhance aqueous dispersibility and tumor specificity. Owing to their compartmentalized design, the hollow mesoporous silica nanoparticles (HMSN) demonstrated enhanced ultrasonic imaging contrast. Combined with the vaporization of the perfluorocarbon perfluoropentane (PFP), the HMSN-encapsulated ZnPc enabled real-time ultrasound monitoring of PDT treatment. In vivo , the innate thermal energy induced vaporization of the DHMSN-carried PFP to significantly amplify ultrasound signals from the tumor site. Results demonstrated biocompatibility, efficient PFP microbubble generation, and robust photocatalytic activity. Collectively, this investigation establishes ultrasound-guided PDT utilizing multi-layer HMSN as a targeted therapeutic strategy for cervical malignancies with mitigated toxicity.

Biodegradable Mg-1%Ca alloy inhibits the growth of cervical cancer

Abstract The traditional treatment for cervical cancer involves aggressive surgery combined with radiotherapy and chemotherapy. Nevertheless, these treatments have certain limitations and side effects, thus breakthroughs and advances are required in cervical cancer therapy. Magnesium alloy is a promising antitumor biomaterial with excellent biocompatibility and biodegradability. However, the potential effects of magnesium alloy on cervical tumors have not been extensively explored. Recent studies have demonstrated that adding a small amount of calcium to the magnesium matrix can reduce grain size and corrosion rate while providing good biocompatibility. We conducted in vivo and in vitro experiments to test the antitumor properties of Mg-1%Ca alloys. The results indicated that the Mg-1%Ca alloy released Mg2+ and OH- more slowly, inhibited the proliferation of SiHa and HeLa cells, induced apoptosis in tumor cells, disrupted the cytoskeleton, and inhibited cell migration and invasion. At the molecular level, Mg-1%Ca alloy significantly activated the mitochondrial apoptosis pathway and inhibited the MAPK/ERK signaling pathway. In the future, Mg-1%Ca may be employed in the treatment of cervical cancer as a novel adjuvant therapeutic material with anticancer function to prevent the occurrence and progression of cancer proliferation and metastasis.