In Vitro Evaluation of the Therapeutic Effects of Dual‐Drug Loaded Spermine‐Acetalated Dextran Nanoparticles Coated with Tannic Acid for Cardiac Applications

Abstract

Myocardial infarction results in a massive loss of cardiomyocytes (CMs). Unfortunately, current therapies are unsuccessful in replacing lost CMs, and thus, there is an urgent need for innovative approaches. Here, a nanosystem based on spermine‐acetalated dextran (AcDXSp) and encapsulating two drug compounds able to stimulate in vitro CMs proliferation is developed. The nanosystem is coated by deposition of a film constituted by tannic acid (TA) and Fe3+ ions. The coating with TA increases the retention of the nanocarrier in cell co‐cultures of CMs and fibroblasts stimulated with transforming growth factor (TGF)‐β, due to the high affinity of TA for components of the cardiac extracellular matrix. The system exhibits biocompatibility toward primary CMs and induces their proliferation, as indicated by the two‐fold increase of CMs in the active cell cycle. At the same time, the presence of TA synergistically helps contrasting fibrosis by reducing profibrotic genes expression, such as collagen 1 and osteopontin, by approximately 80% compared to the control. Overall, the developed nanosystem demonstrates the capability to stimulate CMs proliferation and reduce fibrosis, showing potential benefits for future in vivo applications.

Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification

“…In this context, the targeting ability of cRGD and stealth effect of PEG play important roles in improving the tumor retention rate and circulation time of SRF@FeShik-GOx-cRGD SNs. Because phenolic hydroxyl groups have the strong interaction with elastin and type I collagen in the cardiac extracellular matrix, the accumulation of SRF@FeShik-GOx-cRGD SNs in heart is higher than in other organs. − When the 4T1 tumors reach ∼50 mm 3 , the mice are randomly divided into 6 groups: (i) Saline, (ii) SRF, (iii) FeShik SNs, (iv) SRF@FeShik SNs, (v) SRF@FeShik-GOx SNs, and (vi) SRF@FeShik-GOx-cRGD SNs. Various agents are i.v.…”

Targeted and Infarcted Microenvironment‐Responsive Peptide Therapeutics to Reverse Cardiac Remodeling

“…The high affinity of TA to cardiac ECM was confirmed by a recent study in vitro via culturing myocardial cells. [ 20 ] In order to improve the NPY release in time in the infraction area, the MMP2 stimulated peptide TIMP was incorporated to the complex and the NPY loaded nanostructures (TNT) were formed. We intravenously injected TNT to mice after AMI to reduce surgical trauma and TNT targeted the infarcted myocardium due to TA's strong affinity for cardiac ECM.…”

Progress in Stimuli‐Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases

“…[18] The mechanisms of atherosclerotic plaque formation are complex multistage pathological processes that involve lipoprotein retention, inflammation in local and remote sites, necrosis, angiogenesis, fibrosis, calcification, and others. [17] Selective targeting of these fundamental processes is expected to relieve the heart burden, attenuate ischemic injury, reduce tissue fibrosis, [19] promote cardiac repair and regeneration. [19,20] "Smart" biomaterials hold the capacity to on-demand responses upon activation by particular internal/external stimuli, such as pH levels, redox potential, enzymes, ionic factors, temperature, and electric fields.…”

“…[17] Selective targeting of these fundamental processes is expected to relieve the heart burden, attenuate ischemic injury, reduce tissue fibrosis, [19] promote cardiac repair and regeneration. [19,20] "Smart" biomaterials hold the capacity to on-demand responses upon activation by particular internal/external stimuli, such as pH levels, redox potential, enzymes, ionic factors, temperature, and electric fields. [21] In addition, these biomaterials are easily modified and designed to satisfy the need for precision medicines and ensure efficacy in drug delivery.…”