Background: Cancer is one of the major causes of death and is difficult to cure using existing clinical therapies. Clinical cancer treatments [such as surgery, chemotherapy (CHT), radiotherapy (RT) and immunotherapy (IT)] are widely used but they have limited therapeutic effects and unavoidable side effects. Recently, the development of novel nanomaterials offers a platform for combinational therapy (meaning a combination of two or more therapeutic agents) which is a promising approach for cancer therapy. Recent studies have demonstrated several types of nanomaterials suitable for photothermal therapy (PTT) based on a near-infrared (NIR) light-responsive system. PTT possesses favorable properties such as being low in cost, and having high temporospatial control with minimal invasiveness. However, short NIR light penetration depth limits its functions. Methods: In this review, due to their promise, we focus on inorganic nanomaterials [such as hollow mesoporous silica nanoparticles (HMSNs), tungsten sulfide quantum dots (WS 2 QDs), and gold nanorods (AuNRs)] combining PTT with CHT, RT or IT in one treatment, aiming to provide a comprehensive understanding of PTT-based combinational cancer therapy. Results: This review found much evidence for the use of inorganic nanoparticles for PTTbased combinational cancer therapy. Conclusion: Under synergistic effects, inorganic nanomaterial-based combinational treatments exhibit enhanced therapeutic effects compared to PTT, CHT, RT, IT or PDT alone and should be further investigated in the cancer field.

The extent of participation of side-chain functionalities during the 1,5,7-triazabicyclo[5.4.0]­dec-5-ene (TBD) organobase-catalyzed ring-opening polymerizations (ROP) of six-membered cyclic d-glucose-based carbonates was found to result in significantly different regiochemical outcomes. High regioselectivity was observed for naturally derived poly­(4,6-d-glucose carbonate)­s (PGCs) containing carbonate side chain substituents in the 2- and 3-positions, whereas regioirregularity was found for analogous PGCs with ether side-chain substituents. The backbone connectivities and structural details of these PGCs were examined through a combination of comprehensive 1D and 2D NMR studies on unimers and dimers, verifying the ring-opening preferences and indicating the contribution of side-chain functionalities in regioselective ROP processes. A molecular understanding of the curious role of side-chain functionalities was demonstrated via density functional theory calculations, revealing stabilization effects of intermolecular hydrogen bonding between the side-chain functionalities and TBD in the transition states. Overall, this work provides fundamental insights into the organocatalytic ROP of these specific six-membered asymmetric cyclic glucose carbonates. More importantly, these findings serve as a foundation for future design strategies that incorporate adjacent functionalities within monomers to act as directing groups and impart molecular interactions that define regiochemical ring-opening.

Platelet-like and cylindrical nanostructures from sugarbased polymers are designed to mimic the aspect ratio of bacteria and achieve uroepithelial cell binding and internalization, thereby improving their potential for local treatment of recurrent urinary tract infections. Polymer nanostructures, derived from amphiphilic block polymers composed of zwitterionic poly(D-glucose carbonate) and semicrystalline poly(L-lactide) segments, were constructed with morphologies that could be tuned to enhance uroepithelial cell binding. These nanoparticles exhibited negligible cytotoxicity, immunotoxicity, and cytokine adsorption, while also offering substantial silver cation loading capacity, extended release, and in vitro antimicrobial activity (as effective as free silver cations) against uropathogenic Escherichia coli. In comparison to spherical analogues, cylindrical and platelet-like nanostructures engaged in significantly higher association with uroepithelial cells, as measured by flow cytometry; despite their larger size, platelet-like nanostructures maintained the capacity for cell internalization. This work establishes initial evidence of degradable platelet-shaped nanostructures as versatile therapeutic carriers for treatment of epithelial infections.

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Despite significant progress in synthetic polymer chemistry and in control over tuning the structures and morphologies of nanoparticles, studies on morphologic design of nanomaterials for the purpose of optimizing antimicrobial activity have yielded mixed results. When designing antimicrobial materials, it is important to consider two distinctly different modes and mechanisms of activity—those that involve direct interactions with bacterial cells, and those that promote the entry of nanomaterials into infected host cells to gain access to intracellular pathogens. Antibacterial activity of nanoparticles may involve direct interactions with organisms and/or release of antibacterial cargo, and these activities depend on attractive interactions and contact areas between particles and bacterial or host cell surfaces, local curvature and dynamics of the particles, all of which are functions of nanoparticle shape. Bacteria may exist as spheres, rods, helices, or even in uncommon shapes (e.g., box- and star-shaped) and, furthermore, may transform into other morphologies along their lifespan. For bacteria that invade host cells, multivalent interactions are involved and are dependent upon bacterial size and shape. Therefore, mimicking bacterial shapes has been hypothesized to impact intracellular delivery of antimicrobial nanostructures. Indeed, designing complementarities between the shapes of microorganisms with nanoparticle platforms that are designed for antimicrobial delivery offers interesting new perspectives toward future nanomedicines. Some studies have reported improved antimicrobial activities with spherical shapes compared to non-spherical constructs, whereas other studies have reported higher activity for non-spherical structures (e.g., rod, discoid, cylinder, etc.). The shapes of nano- and microparticles have also been shown to impact their rates and extents of uptake by mammalian cells (macrophages, epithelial cells, and others). However, in most of these studies, nanoparticle morphology was not intentionally designed to mimic specific bacterial shape. Herein, the morphologic designs of nanoparticles that possess antimicrobial activities per se and those designed to deliver antimicrobial agent cargoes are reviewed. Furthermore, hypotheses beyond shape dependence and additional factors that help to explain apparent discrepancies among studies are highlighted. Graphical Abstract