Recent Advances of Multifunctional PLGA Nanocarriers in the Management of Triple-Negative Breast Cancer.

Even though chemotherapy stands as a standard option in the therapy of TNBC, problems associated with it such as anemia, bone marrow suppression, immune suppression, toxic effects on healthy cells, and multi-drug resistance (MDR) can compromise their effects. Nanoparticles gained paramount importance in overcoming the limitations of conventional chemotherapy. Among the various options, nanotechnology has appeared as a promising path in preclinical and clinical studies for early diagnosis of primary tumors and metastases and destroying tumor cells. PLGA has been extensively studied amongst various materials used for the preparation of nanocarriers for anticancer drug delivery and adjuvant therapy because of their capability of higher encapsulation, easy surface functionalization, increased stability, protection of drugs from degradation versatility, biocompatibility, and biodegradability. Furthermore, this review also provides an overview of PLGA-based nanoparticles including hybrid nanoparticles such as the inorganic PLGA nanoparticles, lipid-coated PLGA nanoparticles, cell membrane-coated PLGA nanoparticles, hydrogels, exosomes, and nanofibers. The effects of all these systems in various in vitro and in vivo models of TNBC were explained thus pointing PLGA-based NPs as a strategy for the management of TNBC.

Self-assembled nanomicelles for oral delivery of luteolin utilizing the intestinal lymphatic pathway to target pancreatic cancer.

Pancreatic cancer is one of the major cause of cancer-related deaths worldwide, and is mainly associated with carcinomas of the pancreatic tissue. Current therapies for treating pancreatic cancer have a major drawback related to their low bioavailability and non-specificity, which leads to low therapeutic efficacy and side effects. Luteolin (LUT) has been clinically used for treatment of various types of cancer, although its clinical use has declined owing to its low oral bioavailability. In this work, we prepared an effervescent-based nanocarrier (NG) that rapidly triggers an effervescent reaction and transforms into nanomicelles to modulate the oral bioavailability of the hydrophobic drug Luteolin (LUT). Furthermore, we performed tests to assess its in vitro epithelial cell permeability and cellular internalization on a Caco-2 monolayer. We also performed in vivo toxicity assessment using animal models. Further, we evaluated the nanocarrier system's in vivo efficacy in tumor xenograft pancreatic cancer models. We validated that being pH responsive, our effervescent carrier disassembles at intestinal pH and is absorbed through the intestinal lymphatic system (ILS) to further site-specifically invade the pancreatic cancer cells. Furthermore, the negative surface charge and particle size (450 ± 100 nm) of the nanomicelles helped to internalize LUT through the ILS. We observed that LUT-loaded nanomicelles have significant antipancreatic cancer efficacy by activating caspase-3 activity and downregulating VEGF-A, FAK, TNF-α, and Ki-67. Unlike other drug-delivery systems, we developed noninvasive nanocarrier system has the capability of transporting the hydrophobic drug LUT from the intestine to the tumor site by utilizing the ILS.

The multifaceted role of extracellular vesicles in prostate cancer-a review.

Prostate cancer is the second most prominent form of cancer in men and confers the highest mortality after lung cancer. The term "extracellular vesicles" refers to minute endosomal-derived membrane microvesicles and it was demonstrated that extracellular vesicles affect the environment in which tumors originate. Extracellular vesicles' involvement is also established in the development of drug resistance, angiogenesis, stemness, and radioresistance in various cancers including prostate cancer. Extracellular vesicles influence the general environment, processes, and growth of prostate cancer and can be a potential area that offers a significant lead in prostate cancer therapy. In this review, we have elaborated on the multifaceted role of extracellular vesicles in various processes involved in the development of prostate cancer, and their multitude of applications in the diagnosis and treatment of prostate cancer through the encapsulation of various bioactives.

Folate receptor targeted NIR cleavable liposomal delivery system augment penetration and therapeutic efficacy in breast cancer.

BACKGROUND: Liposomes are predominantly used sorts of nanocarriers for active a targeted delivery through surface functionalization using targeting ligand. The folate receptors are overexpressed in various cancers including breast cancer and because of its binding aptitude specifically to folate receptors, folic acid became the attractive ligand. METHODS: In this research, we have developed a folate and Poly-l-Lysine conjugate and coated this conjugate onto the liposomes. The prepared liposomes were characterized using DLS, FTIR, NMR, SEM, TEM, XRD, AFM, stability and drug release studies. Furthermore, in vitro studies were carried out on FR overexpressed breast cancer cell line. RESULTS: The FA-LUT-ABC-Lip have diameter of 183 ± 3.17 nm with positive surface charge +33.65 ± 3 mV and the drug release studies confirm the NIR responsive payload cleavage. The coated formulation (in presence of NIR light) effectively reduced the IC50 values and kills breast cancer cells through FR mediated internalization and accelerated drug release. Moreover, LUT Formulation shows anticancer effect due to significant inhibition of cell migration and proliferation by regulating VEGF expression and induced apoptosis through the caspase-3 up-regulation. CONCLUSION: It is evident from the in vitro studies that the formulation was found to be very effective and can be explored for triggered and targeted delivery of the substances through active targeting. GENERAL SIGNIFICANCE: Combining receptor mediated drug delivery with triggered release aid in more amounts of drug reaching the target site and achieving enhanced therapeutic activity.

Role of STAT3 in the initiation, progression, proliferation and metastasis of breast cancer and strategies to deliver JAK and STAT3 inhibitors.

INTRODUCTION: Breast cancer (BC) accounts for the majority of cancers among the female population. Anomalous activation of various signaling pathways has become an issue of concern. The JAK-STAT signaling pathway is activated in numerous cancers, including BC. STAT3 is widely involved in BCs, as 40 % of BCs display phosphorylated STAT3. JAK-STAT signaling is crucial for proliferation, survival, metastasis and other cellular events associated with the tumor microenvironment. Hence, targeting this pathway has become an area of interest among researchers. KEY FINDINGS: This review article focuses on the role of STAT3 in the initiation, proliferation, progression and metastasis of BC. The roles of various phytochemicals, synthetic molecules and biologicals against JAK-STAT and STAT3 in various cancers have been discussed, with special emphasis on BC. SIGNIFICANCE: JAK and STAT3 are involved in various phases from initiation to metastasis, and targeting this pathway is a promising approach to inhibit the various stages of BC development and to prevent metastasis. A number of phytochemicals and synthetic and biological molecules have demonstrated potential inhibitory effects on JAK and STAT3, thereby paving the way for the development of better therapeutics against BC.

Organ-restricted delivery through stimuli-responsive nanocarriers for lung cancer therapy.

Lung Cancer (LC) is the malignant tumor of the lungs which is defined by the unrestricted cell development in the lung tissues which if left untreated may migrate to different regions of the body. LC accounts for 12% of the total cancer diagnosis and is among the most occurring malignancies in both genders. Radiotherapy, surgery, and chemotherapy are the treatment options for LC. The obstacles faced by chemotherapy include faster elimination, affecting healthy cells and poor targeting. The application of nanotechnology in drug delivery has gained profound value with the development of various nanoparticulate systems such as nanoparticles (NPs), liposomes etc. Some limitations exhibited by the conventional nanocarriers include leakage of the drug and stability issues. In order to overcome these problems, approaches such as coating of the NPs and use of stimuli-responsive nanocarriers have been utilized. These approaches also aid in boosting pre-existing properties and achieving organ restricted drug delivery. Stimuli-responsive DDS (drug delivery systems) are those systems in which the drug is released or delivered via a stimulus. Due to the reason that cancer tissues exhibit characteristic pH, elevated enzyme levels, these sort of smart nanocarriers have found their application in targeting cancer. Various nanocarriers incorporating various molecules have also been formulated and tested against lung cancer. In this review, we have discussed various classes of stimuli-responsive nanocarriers such as endogenous stimuli-responsive nanocarriers which include pH-responsive nanocarriers, enzyme-responsive nanocarriers and exogenous stimuli-responsive nanocarriers such as thermoresponsive, magnetic-responsive, ultrasound-responsive, photoresponsive nanocarriers along with their application in targeting LC.