Resveratrol (RES) is a naturally existing polyphenol which exhibits anti-oxidant, anti-inflammatory, and anti-cancer properties. In recent years, RES has attracted attention for its synergistic effect with other anti-cancer drugs for the treatment of drug resistant cancers. However, RES faces the issues of poor pharmacokinetics, stability and low solubility which limits its clinical application. In present study, RES has been loaded onto uniformly sized (~60 nm) mesoporous silica nanoparticles (MSNs) to improve its in vitro anti-proliferative activity and sensitization of Docatexal in hypoxia induced drug resistance in prostate cancer. RES was efficiently encapsulated within phosphonate (negatively charged) and amine (positively charged) modified MSNs. The effect of surface functionalization was studied on the loading, in vitro release, anti-proliferative and cytotoxic potential of RES using prostate cancer cell line. At pH 7.4 both free and NH₂-MSNs loaded RES showed burst release which was plateaued with almost 90% of drug released in first 12 h. On the other hand, PO₃-MSNs showed significantly slower release kinetics with only 50% drug release in first 12 h at pH 7.4. At pH 5.5, however, both the PO₃-MSNs and NH₂-MSNs showed significant control over release (around 40% less release compared with free RES in 24 h). Phosphonate modified MSNs significantly enhanced the anti-proliferative potential of RES with an IC₅₀ of 7.15 μM as compared to 14.86 μM of free RES whereas amine modified MSNs didn't affect proliferation with an IC₅₀ value higher than free RES (20.45 μM). Furthermore, RES loaded onto PO₃-MSNs showed robust and dose dependent sensitization of Docatexal in hypoxic cell environment which was comparable to pure RES solution. This study provides an example of applicability of MSNs loaded with polyphenols such as RES as next generation anticancer formulations for treating drug resistant cancers such as prostate cancer.

Photoacoustic (PA) imaging is gaining momentum due to its greater depth of field, low background, and 3D imaging capabilities. However, traditional PA imaging agents (e.g. dyes, quantum dots, etc.) are usually unstable in plasma and bind to serum proteins, and thus cleared rapidly. Because of this, the nanoparticle encapsulation of PA imaging agents is becoming increasingly popular. Therefore, the rational design of carrier nanoparticles for this purpose is necessary for strong imaging signal intensity, high biosafety, and precise targeting. Herein, we systematically evaluate the influence of the chemical and physical surface functionalization of mesoporous silica nanoparticles (MSNs) on the photo-stability, loading, release, and photoacoustic (PA) signal strength of the FDA approved small molecule contrast agent, indocyanine green (ICG). Chemical functionalization involved the modification of MSNs with silanes having amine (NH₂) or phosphonate (PO₃) terminal groups, whereas physical modifications were performed by capping the ICG loaded MSNs with lipid bilayer (LB) or layer-by-layer (LBL) polyelectrolyte coatings. The NH₂-MSNs display the highest ICG mass loading capacity (16.5 wt%) with a limited release of ICG (5%) in PBS over 48 h, while PO₃-MSNs only loaded ICG around 3.5 wt%. The physically modified MSNs (i.e. LBMSNs and LBLMSNs) were vacuum loaded resulting in approximately 9 wt% loading and less than 10% ICG release in 48 h. Pure ICG was highly photo-unstable and showed 20% reduction in photoluminescence (PL) within 3 h of exposure to 800 nm, while the ICG loaded onto functionalized MSNs did not photo-degrade. Among the tested formulations, NH₂-MSNs and LBLMSNs presented 4-fold in vitro PA signal intensity enhancement at a 200 μg mL⁻¹ equivalent ICG dose. Similar to the in vitro PA imaging, NH₂-MSNs and LBLMSNs performed the best when subcutaneously injected into mouse cadavers with 1.29- and 1.43-fold PA signal enhancement in comparison to the pure ICG, respectively.

Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites. Among these, the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones, and thus are highly desired. The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature. In this review, we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine. We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts. As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites, the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites. The inorganic particles that are covered in this review are categorised into two broad types (1) solid (e.g., calcium phosphate, hydroxyapatite, etc.) and (2) porous particles (e.g., mesoporous silica, porous silicon etc.), which are elaborated in detail with recent examples. The review also covers other new types of inorganic material (e.g., 2D inorganic materials, clays, etc.) based polymer composites for tissue engineering applications. Lastly, we provide our expert analysis and opinion of the field focusing on the limitations of the currently used inorganic/organic combination composites and the immense potential of new generation of composites that are in development.