Polymersomes in Drug Delivery─From Experiment to Computational Modeling.

Polymersomes, composed of amphiphilic block copolymers, are self-assembled vesicles that have gained attention as potential drug delivery systems due to their good biocompatibility, stability, and versatility. Various experimental techniques have been employed to characterize the self-assembly behaviors and properties of polymersomes. However, they have limitations in revealing molecular details and underlying mechanisms. Computational modeling techniques have emerged as powerful tools to complement experimental studies and enabled researchers to examine drug delivery mechanisms at molecular resolution. This review aims to provide a comprehensive overview of the state of the art in the field of polymersome-based drug delivery systems, with an emphasis on insights gained from both experimental and computational studies. Specifically, we focus on polymersome morphologies, self-assembly kinetics, fusion and fission, behaviors in flow, as well as drug encapsulation and release mechanisms. Furthermore, we also identify existing challenges and limitations in this rapidly evolving field and suggest possible directions for future research.

Self-Assembly of Poly(Amino Acid)s Mediated by Secondary Conformations.

Self-assembly of block copolymers has recently drawn great attention due to its remarkable performance and wide variety of applications in biomedicine, biomaterials, microelectronics, photoelectric materials, catalysts, etc. Poly(amino acid)s (PAAs), formed by introducing synthetic amino acids into copolymer backbones, are able to fold into different secondary conformations when compared with traditional amphiphilic copolymers. Apart from changing the chemical composition and degree of polymerization of copolymers, the self-assembly behaviors of PAAs could be controlled by their secondary conformations, which are more flexible and adjustable for fine structure tailoring. In this article, we summarize the latest findings on the variables that influence secondary conformations, in particular the regulation of order-to-order conformational changes and the approaches used to manage the self-assembly behaviors of PAAs. These strategies include controlling pH, redox reactions, coordination, light, temperature, and so on. Hopefully, we can provide valuable perspectives that will be useful for the future development and use of synthetic PAAs.

Photoallosteric Polymersomes toward On-Demand Drug Delivery and Multimodal Cancer Immunotherapy.

Allosteric transitions can modulate the self-assembly and biological function of proteins. It remains, however, tremendously challenging to design synthetic allosteric polymeric assemblies with spatiotemporally switchable hierarchical structures and functionalities. Here, a photoallosteric polymersome is constructed that undergoes a rapid conformational transition from ß-sheet to α-helix upon exposure to near-infrared light irradiation. In addition to improving nanoparticle cell penetration and lysosome escape, photoinduced allosteric behavior reconstructs the vesicular membrane structure, which stimulates the release of hydrophilic cytolytic peptide melittin and hydrophobic kinase inhibitor sorafenib. Combining on-demand delivery of multiple therapeutics with phototherapy results in apoptosis and immunogenic death of tumor cells, remold the immune microenvironment and achieve an excellent synergistic anticancer efficacy in vivo without tumor recurrence and metastasis. Such a light-modulated allosteric transition in non-photosensitive polymers provides new insight into the development of smart nanomaterials for biosensing and drug delivery applications.

Ordered Conformation-Regulated Vesicular Membrane Permeability.

In nature, the folding and conformation of proteins can control the cell or organelle membrane permeability and regulate the life activities. Here we report the first example of synthetic polypeptide vesicles that regulate their permeability via ordered transition of secondary conformations, in a manner similar to biological systems. The polymersomes undergo a ß-sheet to α-helix transition in response to reactive oxygen species (ROS), leading to wall thinning without loss of vesicular integrity. The change of membrane structure increases the vesicular permeability and enables specific transport of payloads with different molecular weights. As a proof-of-concept, the polymersomes encapsulating enzymes could serve as nanoreactors and carries for glucose-stimulated insulin secretion in vivo inspired by human glucokinase, resulting in safe and effective treatment of type 1 diabetes mellitus in mouse models. This study will help understand the biology of biomembranes and facilitate the engineering of nanoplatforms for biomimicry, biosensing, and controlled delivery applications.

First Molecular Evidence of Anaplasma phagocytophilum in Rodent Populations of Nanchang, China.

In this study, systematic surveillance of rodent populations in Nanchang of China and determination of Anaplasma phagocytophilum infection in rodents were performed. Between 2011 and 2015, 110,084 rodent snap traps were set in 4 counties and in the city center of Nanchang, China. Finally, 942 rodents were captured, with a relative density of 0.86%. The densities varied considerably by geographical area with Anyi being the most rodent-infested County. Frequently captured rodents were sewer rats (Rattus norvegicus), house mice (Mus musculus), and Rattus flavipectus. The Anaplasma genera were investigated by PCR in 19 live rodents trapped by welded cages in Anyi, 6 rodents were assessed as positive based on amplification of 16S rRNA. Sequence analysis revealed 3 variants of A. phagocytophilum in Nanchang. PCR analysis of the gltA (citrate synthase) gene found 1 sample that was positive for A. phagocytophilum infection. The sequence of A. phagocytophilum gltA gene formed a clade with and showed 99% identity to A. phagocytophilum that has been previously described in rodents from South-Eastern China. Taken together, our research indicated that commensal rodents are potential hosts for A. phagocytophilum and controlling the rodent population may facilitate subsequent prevention of human granulocytic anaplasmosis in Nanchang, China, in the future.

First molecular detection of tick-borne pathogens in dogs from Jiangxi, China.

In this study, blood samples obtained from 162 dogs in Jiangxi, China, were employed in molecular screening of canine tick-borne pathogens by PCR and sequencing. Babesia spp. gene fragment was detected in 12 (7.41%) dogs. All samples were negative for Hepatozoon spp., Ehrlichia canis, Coxiella spp., Borrelia spp., Rickettsia spp. and Anaplasma platys. Species-specific PCR analysis further confirmed that 8 (4.94%) and 4 (2.47%) dogs were infected by Babesia canis vogeli and Babesia gibsoni, respectively. Based on our analyses, Babesia spp. infection in Jiangxi appeared not related to age, gender, breed, usage, activity and health status or tick infestation history of the dogs. This is the first molecular report of Babesia canis vogeli and Babesia gibsoni in dogs from Jiangxi, China.

Knowledge, Attitudes, and Practices (KAP) Relating to Avian Influenza (H10N8) among Farmers' Markets Workers in Nanchang, China.

Three cases of avian influenza virus H10N8 were reported in Nanchang, China, as of April 2014. To identify the knowledge, attitudes, and practices (KAP) related to H10N8 among farmers' market workers, a cross-sectional survey was conducted in 63 farmers' markets in Nanchang. Using the resulting data, characteristics of poultry and non-poultry workers' knowledge, attitudes, and practice were described. Results suggest that interventions targeting high-risk workers should be developed and implemented by public health agencies to prevent the spread of H10N8. Additionally policies that encourage farmers' market workers to receive influenza vaccine should be developed, adopted, and enforced.