Synthesis, Functionalization, and Clinical Translation of Pharmaceutical Biomaterials, Volume II

translation strategies. This invited Research Topic consisted of 7 articles, including 4 original research articles and 3 26 review articles, contributed by 42 researchers worldwide (Total views: 7.3k by November 12, 2022). 27These review articles cover Research Topics discussing nanomaterials and the precise detection and 28 treatment of tumors. One of these reviews provided a systematic summary of all aspects of nano-29 vesicles as drug delivery vectors for cancer therapy: characteristics of polymeric nanovesicles, 30 polymeric nanovesicle synthesis, and recent progress in applying polymeric nanovesicles in antitumor 31 drug delivery (Li et al., 2022). The specialized structures and properties of polymeric nanovesicles 32 exhibited good stability and permeability, easy functionalization, and smart stimulus responsiveness, 33 which made them one of the most promising supramolecular structures for potential applications in 34 delivering drugs, genes, and other therapeutic substances. The other reviews discussed various 35 biomaterials applied to improve pharmacological efficacy and biological safety, such as peptides, 36 nanorobots, or nanoparticles for tumor infarction therapy (Tong et al., 2022), and aptamer 37 nanomaterials as targeted theranostic platforms for ovarian cancers (Jing Zhao1, 2022). Using 38 nanomaterials as carriers to combine therapeutic agents could overcome the shortcomings of a single 39 agent, which showed great potential in presents potential clinical translation. 40In this Research Topic, all the original work showed critical aspects of pharmaceutical biomaterials 41 on their synthesis, functionalization, and potential clinical translation. Emerging pharmaceutical 42 biomaterials were widely used in drug delivery and disease assessment. For instance, to improve 43 therapeutic efficacies, combination therapy using multiple drug agents is necessary, and the 44 employment of biomaterials as drug delivery systems ensures drug delivery efficiency and biological 45 safety. For instance, a reduction-responsive cross-linked nanogel methoxy poly(ethylene glycol)-46 poly(L-phenylalanine-co-L-cystine) (mPEG-(LP-co-LC)) was synthesized using the ring-opening reaction of amino acid N-carboxylanhydride (Liu et al., 2022b). Olaparib and doxorubicin were co-48 loaded by the nanogel, and the drug could quickly release to target cancer cells under the stimulation 49 of a high glutathione concentration in the cancer cells. Compared with free drugs and single-drug-50 loaded nanogels, the dual-drug-co-loaded nanogel exhibited the best anti-cancer efficacy and 51 demonstrated excellent biological safety.Likewise, Poly(lactic-co-glycolic acid)-52 dutasteride/siAR@membrane of human dermal papilla cells (PLGA-DUT/siAR@DPCM) biomimetic 53 nanoparticle simultaneously encapsulating dutasteride and siRNA was used for the synergistic 54 treatment of androgenic alopecia via the suppression of 5α-reductase and knockdown of androgen 55 receptor (Chen et al., 2022). The nanoparticle was coated with the biomimetic membrane of human dermal papilla cells (hDPCs), enabling the nanoparticles to have better hDPC penetration and higher 57 delivery efficiency. 58 Apart from improving the therapeutic outcomes as drug delivery vehicles, some advanced 59 biomaterials also manipulate cell behaviors. For instance, metformin carbon nanodots (MCDs) were 60 synthesized to promote odontoblastic differentiation of dental pulp stem cells (DPSCs) by the pathway 61 of autophagy to achieve functional pulp regeneration (Lu et al., 2022). MCDs were capable of 62 activating autophagy and enhancing the odontogenic differentiation of human dental pulp stem cells 63 (hDPSCs) by upregulating odontoblast gene markers (DMP1, DSPP, RUNX2, and SP7) and expression 64 of proteins (DSPP and DMP1). 65 Lastly, although nanoparticles have been widely studied as drug carriers and therapeutic agents, 66 the evaluation of biological distribution of nanoparticles in tumor microenvironments (TMEs) is still 67 necessary. For example, using vibratome sectioning of tumors provided a method to evaluate the 68 interactions between nanoparticles and the TMEs ex vivo (Liu et al., 2022a). The cell morphology and 69 activity were maintained in vibratome sections, and the distribution of nanocarriers in vibratome tumor 70 sections was similar to that observed in vivo. Ex vivo analysis of tumor tissue slices provided a more 71 convenient and stable method for elucidating the distribution of nanocarriers in the TMEs. 72Overall, the current Research Topic shows the broad applicability of pharmaceutical biomaterials 73 in precisely drug delivery and disease evaluation. Growing evidence suggests that these prospective 74 studies will establish a connection to clinical translation and support the development of biomaterials, 75 bioengineering, biotechnology, and pharmaceutics. 76