Nanoparticles with Active Targeting Ability and Acid Responsiveness for an Enhanced Antitumor Effect of Docetaxel.

Docetaxel (DOC) is commonly used in cancer treatment, especially for breast cancer. However, there are severe side effects in clinical application. In order to deliver docetaxel more effectively, a novel, active targeting acid-responsive polymer called cRGD-PAE-PEG-DSPE was developed. The polymer structure incorporated poly(ethylene glycol) (PEG) as the hydrophilic segment, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) as the hydrophobic segment, and poly(ß-amino ester) (PAE) as the acid-responsive group, which was grafted onto the PEG. Furthermore, c(RGDyC) was grafted onto PAE to confer active targeting capability. Through self-assembly, docetaxel was encapsulated in RAED@DOC. Through in vitro experiments, it was confirmed that RAED@DOC had good serum stability and acid responsiveness, as well as enhanced uptake by MDA-MB-231 cells. Additionally, the antitumor efficiency in vivo and histopathological analysis showed that RAED@DOC exhibited higher antitumor activity and lower systemic toxicity in comparison to free docetaxel. These results suggested that RAED@DOC had considerable potential clinical use.

Zn-MOF hydrogel: regulation of ROS-mediated inflammatory microenvironment for treatment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic and recurrent inflammation disease associated with immune dysfunction. The high level of reactive oxygen species (ROS) causes high oxidative stress and further results in the deterioration of AD. At the same time, the ROS produced by bacterial infection can further aggravate AD. Here, the prepared PVA-based hydrogel (Gel) has a high ROS scavenging ability, and the antibacterial agent Zn-MOF(ZIF-8) loaded into the hydrogel shows a lasting and effective antibacterial activity. Thus, a Zn-MOF hydrogel (Gel@ZIF-8) is prepared to regulate ROS-mediated inflammatory microenvironment. In vitro experiments show that Gel@ZIF-8 has good antibacterial effect and cell biocompatibility. In the AD-induced mouse model, Gel@ZIF-8 can significantly enhance the therapeutic effect, such as reduce the thickness of epidermis, the number of mast cells and IgE antibodies. The results indicate that the ROS-scavenging hydrogel could treat the AD by regulating the inflammatory microenvironment, providing a promising treatment for managing AD.

A Redox-Activatable and Targeted Photosensitizing Agent to Deliver Doxorubicin for Combining Chemotherapy and Photodynamic Therapy.

Currently, tumors have become a serious disease threatening human health and life in modern society. Photo-chemo combination therapy is considered to be an important method to improving the efficiency of tumor treatment, especially in the treatment of multi-drug-resistant tumors. However, the application of photo-chemo combination therapy has been limited by the poor water solubility of photosensitizers, low tumor targeting, and high side effects of chemotherapy drugs. In order to solve these problems, a smart nano drug delivery platform FA-PEG-ss-PLL(-g-Ce6) designed and synthesized by us. The smart nano drug carrier uses folic acid (FA) as the targeting group, polyethylene glycol (PEG) as the hydrophilic end, Ce6-grafted polylysine (PLL(-g-Ce6)) as the hydrophobic end, and Chlorin e6 (Ce6) as the photosensitizer of photodynamic therapy, and it connects PEG to PLL by a redox-responsive cleavable disulfide linker (-ss-). Finally, the combination of tumor chemotherapy and photodynamic therapy (PDT) is realized by loading with anticancer drug doxorubicin (DOX) to the intelligent carrier. In vitro experiments showed that the drug loading content (DLC%) of DOX@FA-PEG-ss-PLL(-g-Ce6) nanoparticles (DOX@FPLC NPs) was as high as 14.83%, and the nanoparticles had good serum stability, reduction sensitivity and hemocompatibility. From the cytotoxicity assays in vitro, we found that under 664 nm laser irradiation DOX@FPLC NPs showed stronger toxicity to MCF-7 cells than did DOX, Ce6 + laser, and DOX + Ce6 + laser. Moreover, the antitumor efficiency in vivo and histopathological analysis showed that DOX@FPLC NPs under 664 nm laser irradiation exhibited higher antitumor activity and lower systemic toxicity than single chemotherapy. These results suggested that the FA-PEG-ss-PLL(-g-Ce6) nano drug delivery platform has considerable potential for the combination of chemotherapy and PDT.

A Novel Polymer Nanoparticle Polydimethyl Diallyl Ammonium Chloride as An Adjuvant Enhances the Immune Response of SARS-CoV-2 Subunit Vaccine.

The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has a significant impact on global health and the economy. It has underscored the urgent need for a stable, easily produced and effective vaccine. This study presents a novel approach using SARS-CoV-2 spike (S) protein-conjugated nanoparticles (NPs) in combination with cyclic GMP-AMP (cGAMP) (S-NPs-cGAMP) as a subunit vaccine. When mice are immunized, the antiserum of S-NPs-cGAMP group exhibits a 16-fold increase in neutralizing activity against a pseudovirus, compared to S protein group. Additionally, S-NPs-cGAMP induces even higher levels of neutralizing antibodies. Remarkably, the vaccine also triggers a robust humoral immune response, as evidenced by a notable elevation in virus-specific IgG and IgM antibodies. Furthermore, after 42 days of immunization, there is an observed increase in specific immune cell populations in the spleen. CD3+CD4+ and CD3+CD8+T lymphocytes, as well as B220+CD19+ and CD3-CD49b+ NK lymphocytes, show an upward trend, indicating a positive cellular immune response. Moreover, the S-NPs-cGAMP demonstrates promising results against the Delta strain and exhibits good cross-neutralization potential against other variants. These findings suggest that pDMDAAC NPs is potential adjuvant and could serve as a versatile platform for future vaccine development.

A hydrogel based on nanocellulose/polydopamine/gelatin used for the treatment of MRSA infected wounds with broad-spectrum antibacterial and antioxidant properties and tissue suitability.

Most wound dressings encounter a series of problems when dealing with the bacterial infection of wounds, for example, the antibacterial and antioxidant capacities, comfort, and mechanical properties are not suitable to meet clinical requirements. Here, we synthesized ε-polylysine-grafted nanocellulose (NCF-EPL) and polydopamine (PDA) nanoparticles and embedded them in genipin-cross-linked gelatin to prepare a hydrogel (NCF-EPL/GTP/PDA). In this system, the embedded NCF-EPL and PDA interact with the gelatin matrix to form a hydrogel with excellent physical properties. The hydrogel has broad-spectrum antibacterial abilities and good antioxidant performance, and it can effectively promote cell proliferation. Full-thickness MRSA-infected skin wound healing experiments clearly show that the NCF-EPL/GTP/PDA hydrogel can significantly accelerate the healing of infected wounds via killing bacteria and reducing inflammation, and secondary damage caused by adhesion during dressing use is effectively avoided. In short, the hydrogel provides a new method for overcoming the shortcomings of traditional dressings, and this approach provides further solutions for the selection of clinical dressings for healing wounds.