<p>A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy</p>

Abstract

Introduction: Currently, the unsatisfactory treatment of cardiac hypertrophy is due to the unbridled myocardial fibrosis. Melatonin has been demonstrated to ameliorate cardiac hypertrophy and its accompanied fibrosis in previous studies. But it is not clinically appealing due to its short-lasting time against the hostile microenvironment when administered orally. Methods: Herein, to address this, poly (lactide) polycarboxybetaine (PLGA-COOH) accompanied by cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs) were used to establish a novel drug delivery and transportation strategy for melatonin via a facile two-step emulsion method. This study characterized these nanoparticles (CHP-mel@SPIONs) and tested their delivery to the hypertrophied heart and their effect on myocardial hypertrophy and fibrosis in an animal model of pressure overload-induced cardiac hypertrophy. Results: The engineered magnetic nanoparticles of CHP-mel@SPIONs were spherical (diameter = 221 ± 13 nm) and had a negative zeta potential of −19.18 ± 3.27 mV. The CHP-mel@SPIONs displayed excellent drug encapsulation capacities of SPIONs (75.27 ± 3.1%) and melatonin (77.69 ± 6.04%) separately, and their magnetic properties were characterized by constructing magnetic hysteresis curves and exhibited no remnant magnetization or coercivity. The animal experiments showed that compared with mel@SPIONs, CHP-mel @SPIONs accumulated more in the heart, especially in the presence of an external magnetic field, with in vivo echocardiography and RT-PCR and histological assessments confirming the amelioration of the myocardial hypertrophy and fibrosis with low drug doses. Conclusion: This simple biocompatible dual-targeting nanoagent may be a potential candidate for the guided clinical therapy of heart disease.

The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

“…These complex interactions between the biological milieu and the nanoparticle depend on multiple factors such as synthetic identity, the biological microenvironment, and the interaction time with the organism. The possibility of functionalizing IONPs with biomolecules such as peptides [ 14 , 15 ], ligands [ 16 ], antibodies [ 17 , 18 ], aptamers [ 19 , 20 ], or RNAs [ 21 ] further enables IONPs to interact with a specific cell type or tissue; for instance, antibody-functionalized IONPs can specifically target antigen-expressing tumor cells, which allows local application of an alternative magnetic field for the induction of magnetic hyperthermia [ 22 ]. Understanding these interactions and how they influence the intended application of the synthesized nanoparticle is critical, as such knowledge not only allows for more rational nanomaterial design but could also enable these previously undiscovered characteristics to be harnessed for combinatorial therapies.…”

Novel Therapeutic Potential of Retinoid-Related Orphan Receptor α in Cardiovascular Diseases

“…A novel biocompatible dual-targeting nanoagent was developed with cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs). Only a low dosage of melatonin carried by the biocompatible dual-targeting nanoagent (CHP-mel@SPIONs) was able to be accumulated in the heart to ameliorate TAC-induced myocardial hypertrophy [ 54 ]. Obviously, this novel compound carries less but transports more drugs to the target organs, which provides an exemplary example for the research and development of RORα-related drugs in the future.…”

Progress and prospect of nanotechnology for cardiac fibrosis treatment

“…In this context, a study conducted by Zhao et al utilized a combination of cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs) for co-targeted delivery of melatonin specifically to the hypertrophied heart tissue, aided by an external magnetic field. 43 They developed a nanoplatform that employed CHP-functionalized SPIONs to deliver melatonin with enhanced specificity to hypertrophied myocardial tissue. While SPIONs possess strong magnetic properties enabling them to be guided to the target, their accuracy in cellular targeting is limited.…”