Unveiling the potential of ursolic acid modified hyaluronate nanoparticles for combination drug therapy in triple negative breast cancer.

Triple negative breast cancer (TNBC) represents the most aggressive and heterogenous disease, and combination therapy holds promising potential. Here, an enzyme-responsive polymeric prodrug with self-assembly properties was synthesized for targeted co-delivery of paclitaxel (PTX) and ursolic acid (UA). Hyaluronic acid (HA) was conjugated with UA, yielding an amphiphilic prodrug with 13.85 mol% UA and a CMC of 32.3 µg/mL. The HA-UA conjugate exhibited ∼14 % and 47 % hydrolysis at pH 7.4 and in tumor cell lysate. HA-UA/PTX NPs exhibited a spherical structure with 173 nm particle size, and 0.15 PDI. The nanoparticles showed high drug loading (11.58 %) and entrapment efficiency (76.87 %) of PTX. Release experiments revealed accelerated drug release (∼78 %) in the presence of hyaluronidase enzyme. Cellular uptake in MDA-MB-231 cells showed enhanced uptake of HA-UA/PTX NPs through CD44 receptor-mediated endocytosis. In vitro, HA-UA/PTX NPs exhibited higher cytotoxicity, apoptosis, and mitochondrial depolarization compared to PTX alone. In vivo, HA-UA/PTX NPs demonstrated improved pharmacokinetic properties, with 2.18, 2.40, and 2.35-fold higher AUC, t1/2, and MRT compared to free PTX. Notably, HA-UA/PTX NPs exhibited superior antitumor efficacy with a 90 % tumor inhibition rate in 4T1 tumor model and low systemic toxicity, showcasing their significant potential as carriers for TNBC combination therapy.

Patient Perspectives After Surgery-Related Complications Among Breast Cancer Patients from a LMIC.

Long-term quality of life in breast cancer patients has been studied and published regularly. However, the lived experiences of patients who develop complications after surgery are not well understood. Determining this experience of patients is challenging in most low- and middle-income countries where the majority of patients belong to poor strata of society and are uneducated. We aimed to explore the thoughts, feelings, and experiences of patients with surgery-related complications after breast cancer surgery. Purposive sampling was used to identify patients who developed any postoperative complication, and semi-structured interviews were conducted. Common patterns of patient experiences were identified and analyzed using descriptive thematic analysis. Twenty-eight patients out of 210 developing complications postoperatively were identified. The median age was 48 years (range 32-65 years). The majority (n = 26) were housewives, educated below the primary level (n = 11) and below the poverty line (n = 13). Complications included seroma (n = 17), flap necrosis and infection (n = 5), and hematoma (n = 1). Seven domains emerged from the interviews-knowledge of complications, psychological impact, burden, disruptiveness, social impact, relationship with the surgical team, and suggestions to improve the experience. The themes identified in the present study provide insights into the lived experiences and can inform the future development of patient-reported outcome measures and quality improvement programs, including more effective pre-operative counseling and consent. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01721-z.

Hepatocellular carcinoma: Preclinical and clinical applications of nanotechnology with the potential role of carbohydrate receptors.

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer; accounts for 75-85% of cases. The treatment and management of HCC involve different sanative options like surgery, chemotherapy, immunotherapy, etc. Recently, various advancements have been introduced for the diagnosis and targeting of hepatic tumor cells. Among these, biomarkers are considered the primary source for the diagnosis and differentiation of tumor cells. With the advancement in the field of nanotechnology, different types of nanocarriers have been witnessed in tumor targeting. Nanocarriers such as nanoparticles, liposomes, polymeric micelles, nanofibers, etc. are readily prepared for effective tumor targeting with minimal side-effects. The emergence of various approaches tends to improve the effectiveness of these nanocarriers as demonstrated in ample clinical trials. This review focuses on the significant role of carbohydrates such as mannose, galactose, fructose, etc. in the development, diagnosis, and therapy of HCC. Hence, the current focus of this review is to acknowledge various perspectives regarding the occurrence, diagnosis, treatment, and management of HCC.

Decision-Making Dilemma in Preoperative Cardiac Evaluation: Should We Turn the Page or Close the Book?

Coronary artery disease is one of the most dreadful and life-threatening diseases out of all cardiac diseases. The diagnosis and management of coronary artery disease comprise stepwise approaches. All these approaches are mostly guideline-driven. While the majority of the time, guidelines help us take the most appropriate care, exceptions do exist. For example, patients may have unusual risk factors and abnormal test results; however, they do not fit into the guideline algorithm to proceed further.  This case report of a 68-year-old male patient depicts a true example of such a situation. He presented to the cardiologist's office for pre-operative cardiac evaluation for urological surgery. In view of associated risk factors, an exercise stress test was done, which showed critical abnormalities. As per the pre-operative cardiac assessment guidelines, the patient did not meet the criteria for further testing. However, a clinician's strong judgment and persistent negotiation superseded those barriers. Given critical abnormalities of the exercise stress test, the patient underwent cardiac catheterization. He was found to have triple vessel disease on cardiac catheterization. The scheduled surgery was withheld, and the patient underwent a coronary artery bypass graft. This life-threatening condition could have been easily missed if only the guidelines were to be followed. While guidelines cover a significant portion of the bell curve, this case report represents the importance of not missing the tail ends of the curve. It enhances the importance of thinking out of the box based on clinical training and expertise.

Manikya Bhasma is a nanomedicine to affect cancer cell viability through induction of apoptosis.

BACKGROUND: Ayurveda is an ancient medicine system practiced in the Indian sub-continent. Ayurvedic Bhasma is incinerated herbo-metallic/mineral preparations that consist of the particles in the range of nano/micrometers with therapeutic effects against different diseases. Manikya Bhasma (MB) is composed of purified ruby, orpiment, and purified arsenic sulfide. OBJECTIVE: This study was conducted to identify the potential of MB as a nanomedicine that can be used for the treatment of cancer. MATERIALS AND METHODS: Biophysical characterization to determine the morphology and composition of bhasma particles was done using several techniques such as DLS, FTIR, FETEM, FESEM, EDX, and XRD. Cell viability assays were conducted to identify the cytotoxic effect of MB against different cancer cell lines and also to determine the mode of death caused by MB. RESULTS: The biophysical characterization of MB indicates that it is crystalline with a particle size of 70 nm. MB exhibits anticancer activity against MDAMB-231, HeLa, HCT-116, DLD-1, MG-63 cancer cells with an IC50 in the range of 105-155 µg/mL. MB induces oxidative stress in cancer cells, which in turn affects their cell-cycle with an accumulation of cells in the G1-phase. Also, apoptosis induced by MB involves loss of mitochondrial membrane potential, the release of Cyt c, activation of caspases, and DNA degradation. CONCLUSION: Our study highlights the dual potential of MB as a nano-carrier to deliver the drugs and exerting cytotoxic effects against cancer cells.