scholarly journals Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles

2021 ◽  
Vol 118 (7) ◽  
pp. e2020575118
Author(s):  
Jamie K. Hu ◽  
Hee-Won Suh ◽  
Munibah Qureshi ◽  
Julia M. Lewis ◽  
Sharon Yaqoob ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Surgical Excision ◽  
Tumor Burden ◽  
Nonsurgical Treatment ◽  
Matrix Proteins ◽  
Poly Lactic Acid ◽  
Covalent Bonds ◽  
Cpg Oligodeoxynucleotides ◽  
Skin Cancers ◽  
Vicinal Diols

Keratinocyte-derived carcinomas, including squamous cell carcinoma (SCC), comprise the most common malignancies. Surgical excision is the therapeutic standard but is not always clinically feasible, and currently available alternatives are limited to superficial tumors. To address the need for a nonsurgical treatment for nodular skin cancers like SCC, we developed a bioadhesive nanoparticle (BNP) drug delivery system composed of biodegradable polymer, poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG), encapsulating camptothecin (CPT). Nanoparticles (NPs) of PLA-HPG are nonadhesive NPs (NNPs), which are stealthy in their native state, but we have previously shown that conversion of the vicinal diols of HPG to aldehydes conferred NPs the ability to form strong covalent bonds with amine-rich surfaces. Herein, we show that these BNPs have significantly enhanced binding to SCC tumor cell surfaces and matrix proteins, thereby significantly enhancing the therapeutic efficacy of intratumoral drug delivery. Tumor injection of BNP-CPT resulted in tumor retention of CPT at ∼50% at 10 d postinjection, while CPT was undetectable in NNP-CPT or free (intralipid) CPT-injected tumors at that time. BNP-CPT also significantly reduced tumor burden, with a portion (∼20%) of BNP-CPT–treated established tumors showing histologic cure. Larger, more fully established PDV SCC tumors treated with a combination of BNP-CPT and immunostimulating CpG oligodeoxynucleotides exhibited enhanced survival relative to controls, revealing the potential for BNP delivery to be used along with local tumor immunotherapy. Taken together, these results indicate that percutaneous delivery of a chemotherapeutic agent via BNPs, with or without adjuvant immunostimulation, represents a viable, nonsurgical alternative for treating cutaneous malignancy.

Imine Based Self-Healing Hydrogel Triggered by Periodate

2020 ◽  
Author(s):  
Alexis Wolfel ◽  
Cecilia Inés Alvarez Igarzabal ◽  
Marcelo Ricardo Romero
Keyword(s):  
Functional Groups ◽  
Time Window ◽  
Crosslinking Reaction ◽  
Self Healing ◽  
Swelling Properties ◽  
Covalent Bonds ◽  
Smart Systems ◽  
Primary Amino ◽  
Vicinal Diols ◽  
Aldehyde Groups

<p>Design of materials with novel sensitivities and smart behaviour is important for the development of smart systems with automated responsiveness. We have recently reported the synthesis of hydrogels, cross-linked by <i>N,N'</i>-diallyltartardiamide (DAT). The covalent DAT-crosslinking points have vicinal diols which can be easily cleaved with periodate, generating valuable a-oxo-aldehyde functional groups, useful for further chemical modification. Based on those findings, we envisioned that a self-healable hydrogel could be obtained by incorporation of primary amino functional groups, from <a>2-aminoethyl methacrylate </a>hydrochloride (AEMA), coexisting with DAT into the same network. The a-oxo-aldehyde groups generated after the reaction with periodate would arise in the immediate environment of amine groups to form imine cross-links. For this purpose, DAT-crosslinked hydrogels were synthesized and carefully characterized. The cleavage of DAT-crosslinks with periodate promoted changes in the mechanical and swelling properties of the materials. As expected, a self-healing behavior was observed, based on the spontaneous formation of imine covalent bonds. In addition, we surprisingly found a combination of fast vicinal diols cleavage and a low speed self-crosslinking reaction by imine formation. Consequently, it was found a time-window in which a periodate-treated polymer was obtained in a transient liquid state, which can be exploited to choose the final shape of the material, before automated gelling. The singular properties attained on these hydrogels could be useful for developing sensors, actuators, among other smart systems.</p>

scholarly journals A comprehensive study on 2D, 3D and solid tumor environment to explore a multifunctional biogenic nanoconjugate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
B. S. Unnikrishnan ◽  
G. U. Preethi ◽  
T. T. Sreelekha
Keyword(s):  
Drug Delivery ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Tumor Burden ◽  
Oxide Nanoparticles ◽  
Cell Internalization ◽  
Tumor Environment ◽  
D Cell ◽  
Cancer Spheroids ◽  
Comprehensive Study

AbstractEmergence of nanotechnology created a drastic change in the field of cancer therapy due to their unique features in drug delivery and imaging. Polysaccharide based nanoparticles have received extensive attention in recent years as promising nanoparticle mediated drug delivery systems. Polysaccharides are endorsed with versatile merits including high drug encapsulation efficiency, efficient drug protection against chemical or enzymatic degradation, unique ability to create a controlled release and cellular internalization. In the current study, we have fabricated doxorubicin-loaded carboxymethylated PST001 coated iron oxide nanoparticles (DOX@CM-PST-IONPs) for better management of cancer. CM-PST coated iron oxide nanoparticles co-encapsulated with chemotherapeutic drug doxorubicin, can be utilized for targeted drug delivery. Biocompatible and non-toxic nanoconjugates was found to be effective in both 2-D and 3-D cell culture system with efficient cancer cell internalization. The bench-marked potential of CM-PIONPs to produce reactive oxygen species makes it a noticeable drug delivery system to compact neoplasia. These nanoconjugates can lay concrete on a better way for the elimination of cancer spheroids and tumor burden.

scholarly journals Protein-Based Nanohydrogels for Bioactive Delivery

2021 ◽  
Vol 9 ◽  
Author(s):  
Subhash Chander ◽  
Giriraj T. Kulkarni ◽  
Neerupma Dhiman ◽  
Harsha Kharkwal
Keyword(s):  
Drug Delivery ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Biological Fluids ◽  
Three Dimensional ◽  
Covalent Bond ◽  
Ionic Concentration ◽  
Covalent Bonds ◽  
Encapsulation Process ◽  
Insightful Analysis

Hydrogels possess a unique three-dimensional, cross-linked network of polymers capable of absorbing large amounts of water and biological fluids without dissolving. Nanohydrogels (NGs) or nanogels are composed of diverse types of polymers of synthetic or natural origin. Their combination is bound by a chemical covalent bond or is physically cross-linked with non-covalent bonds like electrostatic interactions, hydrophobic interactions, and hydrogen bonding. Its remarkable ability to absorb water or other fluids is mainly attributed to hydrophilic groups like hydroxyl, amide, and sulphate, etc. Natural biomolecules such as protein- or peptide-based nanohydrogels are an important category of hydrogels which possess high biocompatibility and metabolic degradability. The preparation of protein nanohydrogels and the subsequent encapsulation process generally involve use of environment friendly solvents and can be fabricated using different proteins, such as fibroins, albumin, collagen, elastin, gelatin, and lipoprotein, etc. involving emulsion, electrospray, and desolvation methods to name a few. Nanohydrogels are excellent biomaterials with broad applications in the areas of regenerative medicine, tissue engineering, and drug delivery due to certain advantages like biodegradability, biocompatibility, tunable mechanical strength, molecular binding abilities, and customizable responses to certain stimuli like ionic concentration, pH, and temperature. The present review aims to provide an insightful analysis of protein/peptide nanohydrogels including their preparation, biophysiochemical aspects, and applications in diverse disciplines like in drug delivery, immunotherapy, intracellular delivery, nutraceutical delivery, cell adhesion, and wound dressing. Naturally occurring structural proteins that are being explored in protein nanohydrogels, along with their unique properties, are also discussed briefly. Further, the review also covers the advantages, limitations, overview of clinical potential, toxicity aspects, stability issues, and future perspectives of protein nanohydrogels.

scholarly journals Stem Cells as a Target for the Delivery of Active Molecules to Skin by Topical Administration

2020 ◽  
Vol 21 (6) ◽  
pp. 2251
Author(s):  
Hamid-Reza Ahmadi-Ashtiani ◽  
Parisa Bishe ◽  
Anna Baldisserotto ◽  
Piergiacomo Buso ◽  
Stefano Manfredini ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Stem Cells ◽  
Topical Administration ◽  
Therapeutic Interventions ◽  
Skin Cancers ◽  
Basic And Applied Research ◽  
Hair Follicle Growth ◽  
Novel Drug ◽  
Physical And Chemical ◽  
Cell Gene

Cutaneous stem cells, gained great attention in the field of regenerative medicine as a potential therapeutic target for the treatment of skin and hair disorders and various types of skin cancers. Cutaneous stem cells play a key role in several processes like the renovation of skin structures in the condition of homeostasis and after injuries, the hair follicle growth and the reconstruction and production of melanocytes. Thus, gaining effective access to skin stem cells for therapeutic interventions that often involve active molecules with non-favorable characteristics for skin absorption is a valuable achievement. The topical route with high patient compliance and several other benefits is gaining increasing importance in basic and applied research. However, the major obstacle for topical drug delivery is the effective barrier provided by skin against penetration of the vast majority of exogenous molecules. The research in this field is focusing more and more on new strategies to circumvent and pass this barrier effectively. In this article the existing approaches are discussed considering physical and chemical methods along with utilization of novel drug delivery systems to enhance penetration of drugs to the skin. In particular, attention has been paid to studies finalized to the delivery of molecules to cutaneous stem cells with the aim of transferring signals, modulating their metabolic program, inducing physiological modifications and stem cell gene therapy.

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