Many therapeutically active molecules are non-soluble in aqueous systems, chemically and biologically fragile or present severe side effects. Lipid-based nanoparticle (LBNP) systems represent one of the most promising colloidal carriers for bioactive organic molecules. Their current application in oncology has revolutionized cancer treatment by improving the antitumor activity of several chemotherapeutic agents. LBNPs advantages include high temporal and thermal stability, high loading capacity, ease of preparation, low production costs, and large-scale industrial production since they can be prepared from natural sources. Moreover, the association of chemotherapeutic agents with lipid nanoparticles reduces active therapeutic dose and toxicity, decreases drug resistance and increases drug levels in tumor tissue by decreasing them in healthy tissue. LBNPs have been extensively assayed in in vitro cancer therapy but also in vivo, with promising results in some clinical trials. This review summarizes the types of LBNPs that have been developed in recent years and the main results when applied in cancer treatment, including essential assays in patients.

https://www.mdpi.com/2079-4991/9/4/638/pdf

Lipid-Based Nanoparticles: Application and Recent Advances in Cancer Treatment.

Ultrasound (US)-triggered sonodynamic therapy (SDT), as a promising noninvasive therapeutic modality, has received ever-increasing attention in recent years. Its specialized chemical agents, named sonosensitizers, are activated by low-intensity US to produce lethal reactive oxygen species (ROS) for oncotherapy. Compared with phototherapeutic strategies, SDT provides many noteworthy opportunities and benefits, such as deeper penetration depth, absence of phototoxicity, and fewer side effects. Nevertheless, previous studies have also demonstrated its intrinsic limitations. Thanks to the facile engineering nature of nanotechnology, numerous novel nanoplatforms are being applied in this emerging field to tackle these intrinsic barriers and achieve continuous innovations. In particular, the combination of SDT with other treatment strategies has demonstrated a superior efficacy in improving anticancer activity relative to that of monotherapies alone. Therefore, it is necessary to summarize the nanomaterial-assisted combinational sonodynamic cancer therapy applications. Herein, the design principles in achieving synergistic therapeutic effects based on nanomaterial engineering methods are highlighted. The ultimate goals are to stimulate the design of better-quality combined sonodynamic treatment schemes and provide innovative ideas for the perspectives of SDT in promoting its future transformation to clinical application.

Recent Advances in Nanomaterial-Assisted Combinational Sonodynamic Cancer Therapy.

CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans

Ellagic acid is a common metabolite present in many medicinal plants and vegetables. It is present either in free form or as part of more complex molecules (ellagitannins), which can be metabolized to liberate ellagic acid and several of its metabolites, including urolithins. While ellagic acidʼs antioxidant properties are doubtless responsible for many of its pharmacological activities, other mechanisms have also been implicated in its various effects, including its ability to reduce the lipidemic profile and lipid metabolism, alter pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, interleukin-6), and decrease the activity of nuclear factor-κB while increasing nuclear factor erythroid 2-related factor 2 expression. These events play an important role in ellagic acidʼs anti-atherogenic, anti-inflammatory, and neuroprotective effects. Several of these activities, together with the effect of ellagic acid on insulin, glycogen, phosphatases, aldose reductase, sorbitol accumulation, advanced glycation end-product formation, and resistin secretion, may explain its effects on metabolic syndrome and diabetes. In addition, results from recent research have increased the interest in ellagic acid, both as a potential protective agent of the liver and skin and as a potential anticancer agent, due to the specific mechanisms affecting cell proliferation, apoptosis, DNA damage, and angiogenesis and its aforementioned anti-inflammatory properties. Taken together, these effects make ellagic acid a highly interesting compound that may contribute to different aspects of health; however, more studies are needed, especially on the compoundʼs pharmacokinetic profile. In this review, we selected papers published from 2005 to the present.

/pdf/a-pharmacological-update-of-ellagic-acid-c8uajcjr0q.pdf

A Pharmacological Update of Ellagic Acid

The delivery of drugs to tumors by nanoparticles is a rapidly growing field. However, the complex tumor microenvironment (TME) barriers greatly hinder drug delivery to tumors. In this study, we first summarized the barriers in TME, including anomalous vasculature, rigid extracellular matrix, hypoxia, acidic pH, irregular enzyme level, altered metabolism pathway and immunosuppressive conditions. To overcome these barriers, many strategies have been developed, such as modulating TME, active targeting by ligand modification and biomimetic strategies, and TME-responsive drug delivery strategies to improve nanoparticle penetration, cellular uptake and drug release. Although extensive progress has been achieved, there are still many challenges, which are discussed in the last section. Overall, we carefully discuss the landscape of TME, development for improving drug delivery, and challenges that need to be further addressed.

https://pubs.rsc.org/en/content/articlepdf/2020/tb/d0tb00649a

Overcoming the biological barriers in the tumor microenvironment for improving drug delivery and efficacy

Fibrotic stroma and tumor-promoting pancreatic stellate cells (PSCs), critical characters in the pancreatic ductal adenocarcinoma (PDA) microenvironment, promote a tumor-facilitating environment that simultaneously prevents drug penetration into tumor foci and stimulates tumor growth. Nab-PTX, a human serum albumin (HSA) nanoparticle of paclitaxel (PTX), indicates enhanced matrix penetration in PDA probably due to its small size in vivo and high affinity of HSA with secreted protein acidic and rich in cysteine (SPARC), overexpressed in the PDA stroma. However, this HSA nanoparticle shows poor drug blood retention because of its weak colloidal stability in vivo, thus resulting in insufficient drug accumulation within tumor. Encapsulating HSA nanoparticles into the internal aqueous phase of ordinary liposomes improves their blood retention and the following tumor accumulation, but the large 200 nm size and shielding of HSA in the interior might make it difficult for this hybrid nanomedicine to penetrate the...

Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer.

Promoting tumor angiogenesis effectively and specifically to resolve tumor-associated hypoperfusion holds promise for improving pancreatic cancer therapy. Herein, a doxorubicin (DOX) loaded smart liposome, MC-T-DOX, is constructed, that carries appropriately low-density cilengitide, an αvβ3 integrin-specific Arg-Gly-Asp (RGD)-mimetic cyclic peptide, via a membrane type 1-matrix metalloproteinase (MT1-MMP) cleavable peptide. After being administered systemically in a hypoperfused pancreatic cancer mouse model at a low dose of cilengitide, the proangiogenic activity of MC-T-DOX is specifically "turned on" in tumor vessels through cleavage by MT1-MMP on tumor endothelial cells to release cilengitide. This locally released cilengitide increases tumor blood perfusion, thereby improving the accumulation and distribution of MC-T-DOX in the tumor site. The loaded-DOX then displays enhanced penetration and increased cellular uptake upon heat-triggered release from MC-T-DOX in the tumor interstitium, contributing to the improved tumor therapy efficacy. Therefore, the strategy of combining the modulation of tumor vascular promotion with smart nanodrug delivery represents a promising approach to improving drug delivery and therapeutic efficacy in a wide range of hypoperfused tumors.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/advs.201902746

MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy

Smart Tumor Microenvironment-Responsive Nanotheranostic Agent for Effective Cancer Therapy

Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells

Yan Wei

Papers

Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer.

MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy

Smart Tumor Microenvironment-Responsive Nanotheranostic Agent for Effective Cancer Therapy

Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells