Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer.

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

Recent Progress in Diboronic-Acid-Based Glucose Sensors.

Non-enzymatic sensors with the capability of long-term stability and low cost are promising in glucose monitoring applications. Boronic acid (BA) derivatives offer a reversible and covalent binding mechanism for glucose recognition, which enables continuous glucose monitoring and responsive insulin release. To improve selectivity to glucose, a diboronic acid (DBA) structure design has been explored and has become a hot research topic for real-time glucose sensing in recent decades. This paper reviews the glucose recognition mechanism of boronic acids and discusses different glucose sensing strategies based on DBA-derivatives-based sensors reported in the past 10 years. The tunable pKa, electron-withdrawing properties, and modifiable group of phenylboronic acids were explored to develop various sensing strategies, including optical, electrochemical, and other methods. However, compared to the numerous monoboronic acid molecules and methods developed for glucose monitoring, the diversity of DBA molecules and applied sensing strategies remains limited. The challenges and opportunities are also highlighted for the future of glucose sensing strategies, which need to consider practicability, advanced medical equipment fitment, patient compliance, as well as better selectivity and tolerance to interferences.

Cancer vaccines: Targeting KRAS-driven cancers.

Introduction: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers.Areas covered: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers.Expert opinion: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.

A promising treatment option for refractory male primary choriocarcinoma: report of two cases.

Male primary choriocarcinoma is a rare and invasive malignant neoplasm for which traditional chemotherapy has limited efficacy. Pembrolizumab is a humanized monoclonal anti-programmed death-1 antibody that has antitumor activity in numerous malignancies. The diagnosis and treatment of two cases of advanced male primary choriocarcinoma were retrospectively analyzed and relevant literature was reviewed to discuss the prognosis and the efficacy of different treatments, including pembrolizumab. The first patient, who presented with cough and hemoptysis, was diagnosed with primary mediastinal choriocarcinoma. He initially responded to the first-line chemotherapy of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine, but eventually developed brain metastases. The patient did not respond to the second-line chemotherapy comprising paclitaxel and cisplatin, and he died 6.5 months after diagnosis. The second patient experienced repeated episodes of abdominal pain and was diagnosed with primary neck choriocarcinoma. He received chemotherapy regimens similar to those of the first patient. However, imaging showed no significant changes and his clinical symptoms were not improved. Immunohistochemistry showed that the expression of programmed death ligand 1 on the tumor cells was 40%, and he was administered pembrolizumab combined with chemotherapy. He achieved complete response and was subsequently switched to pembrolizumab maintenance monotherapy. He is still alive without evidence of disease 36 months after diagnosis. To our knowledge, this is the first case of advanced male primary choriocarcinoma successfully treated with pembrolizumab combined with chemotherapy. Advanced male primary choriocarcinoma is highly aggressive and insensitive to chemotherapy. Pembrolizumab may provide a promising treatment option to improve patient outcomes.