Plant Pollen Grains:A Move Towards Green Drug and Vaccine Delivery Systems

Pollen grains and plant spores have emerged as innovative biomaterials for various applications such as drug/vaccine delivery,catalyst support,and the removal of heavy metals.The natural microcapsules comprising spore shells and pollen grain are designed for protecting the genetic materials of plants from exterior impairments.Two layers make up the shell,the outer layer(exine)that comprised largely of sporopollenin,and the inner layer(intine)that built chiefly of cellulose.These microcapsule shells,namely hollow sporopollenin exine capsules have some salient features such as homogeneity in size,non-toxic nature,resilience to both alkalis and acids,and the potential to withstand at elevated temperatures;they have displayed promising potential for the microencapsulation and the controlled drug delivery/release.The important attribute of mucoadhesion to intestinal tissues can prolong the interaction of sporopollenin with the intestinal mucosa directing to an augmented effectiveness of nutraceutical or drug delivery.Here,current trends and prospects related to the application of plant pollen grains for the delivery of vaccines and drugs and vaccine are discussed.

Mucosal vaccine delivery:A focus on the breakthrough of specific barriers

Mucosal vaccines can effectively induce an immune response at the mucosal site and form the first line of defense against microbial invasion.The induced mucosal immunity includes the proliferation of effector T cells and the production of IgG and IgA antibodies,thereby effectively blocking microbial infection and transmis sion.However,after a long period of development,the transformation of mucosal vaccines into clinical use is still relatively slow.To date,fewer than ten mucosal vaccines have been approved.Only seven mucosal vaccines against coronavirus disease 2019(COVID-19) are under investigation in clinical trials.A representative vaccine is the adenovirus type-5 vectored COVID-19 vaccine(Ad5-nCoV) developed by Chen and coworkers,which is currently in phase Ⅲ clinical trials.The reason for the limited progress of mucosal vaccines may be the complicated mucosal barriers.Therefore,this review summarizes the characteristics of mucosal barriers and highlights strategies to overcome these barriers for effective mucosal vaccine delivery.

Nanotechnology and vaccine development

Despite the progress of conventional vaccines,improvements are clearly required due to concerns about the weak immunogenicity of these vaccines,intrinsic instability in vivo,toxicity,and the need for multiple administrations.To overcome such problems,nanotechnology platforms have recently been incorporated into vaccine development.Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses.This advantage is attributable to the nanoscale particle size,which facilitates uptake by phagocytic cells,the gut-associated lymphoid tissue,and the mucosa-associated lymphoid tissue,leading to efficient antigen recognition and presentation.Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors,thereby stimulating specific and selective immune responses.In this review,we introduce recent advances in nanocarrierbased vaccine delivery systems,with a focus on the types of carriers,including liposomes,emulsions,polymer-based particles,and carbon-based nanomaterials.We describe the remaining challenges and possible breakthroughs,including the development of needlefree nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

Using Bacterial Vectors for Probable Vaccines: From Molecular Mechanism to Cancer Therapy

Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.

Advanced materials for the delivery of vaccines for infectious diseases

Infectious diseases are an increasing threat to global biosafety.Vaccination is the most effective and costefficient method for preventing and controlling infectious diseases.The development of new vaccines is inextricably linked to the advancement of materials that serve as essential components of vaccines,such as antigens,adjuvants,and their carriers.The physicochemical and biological properties of vaccines-such as the kinetics of antigen retention and presentation-are determined by the material compositions of vaccines and carriers,affecting the overall efficacy.The sustained release of antigens prolongs their retention time in germinal centers and improves humoral immune responses.Pulsatile release that imitates clinical dosing regimens can improve patient adherence to vaccination,affording increased vaccine coverage.Herein,we review progress of materials innovation on altering vaccine release kinetics,which affects the overall vaccine efficacy,safety,and compliance.

Laser facilitates vaccination

Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces:to improve vaccine efficacy without compromising safety.Harnessing the specific effects of laser on biological systems,a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way.The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical e®ects with no foreign chemicals administered into the body.Here,we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

Oral vaccination of mice against rodent malaria with recombinant Lactococcus lactis expressing MSP-1_(19)

AIM： To construct the recombinant Lactococcus/actis as oral delivery vaccination against malaria. METHODS： The C-terminal 19-ku fragments of MSP1 （MSP-119） of Plasmodium yoelii265-BY was expressed in L. lactis and the recombinant L. lact/s was administered orally to BALB/c and C57BL/6 mice. After seven interval vaccinations within 4 wk, the mice were challenged with P. yoelii 265-BY parasites of erythroo/tic stage. The protective efficacy of recombinant L. lactiswas evaluated. RESULTS： The peak parasitemias in average for the experiment groups of BALB/c and C57BL/6 mice were 0.8± 0.4% and 20.8±26.5%, respectively, and those of their control groups were 12.0±0.8% and 60.8±9.6%, respectively. None of the BALB/c mice in both experimental group and control group died during the experiment. However, all the C57BL/6 mice in the control group died within 23 d and all the vaccinated mice survived well. CONCLUSION： The results imply the potential of recombinant L. lactis as oral delivery vaccination against malaria.

Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors

Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment,in addition to improving oral bioavailability relative to other means of delivery of oral drugs.Here,inspired by the specific invasion route of intestinal microorganisms,we pioneered an immune-awakening Saccharomyces-inspired mesoporous silicon nanoparticle(yMSN)for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic pathway.Encouragingly,yMSN high-loaded tumor-specific antigens(OVA,11.9%)and anti-tumor drugs(Len,28.6%)with high stability,namely Len/OVA/yMSN,efficiently co-delivered OVA and Len to their desired target sites.Moreover,yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages,strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor microenvironment.Surprisingly,Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing mice.This high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment,and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases.

Intranasal and oral vaccination with protein-based antigens： advantages, challenges and formulation strategies

Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low im- munogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.

Bioengineering of nano metal-organic frameworks for cancer immunotherapy

Immunotherapy techniques,such as immune checkpoint inhibitors,chimeric antigen receptor(CAR)T cell therapies and cancer vaccines,have been burgeoning with great success,particularly for specific cancer types.However,side effects with fatal risks,dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy.Nano metal-organic frameworks(nMOFs),with an accurate structure and a narrow size distribution,are emerging as a solution to these problems.In addition to their function of temporospatial delivery,a large library of their compositions,together with flexibility in chemical interaction and inherent immune efficacy,offers opportunities for various designs of nMOFs for immunotherapy.In this review,we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies.We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation.Finally,a prospect of nMOFs in cancer immunotherapy will be discussed.