Hetero-Trifunctional Malonate-Based Nanotheranostic System for Targeted Breast Cancer Therapy

Abstract

Designing multifunctional linkers is crucial for tricomponent theranostic targeted nanomedicine development as they are essential to enrich polymeric systems with different functional moieties. Herein, we have obtained a hetero-trifunctional linker from malonic acid and demonstrated its implication as an amphiphilic targeted nanotheranostic system (CB DX UN PG FL). We synthesized it with varying hydrophilic segment to finetune the hydrophobic/hydrophilic ratio to optimize its selfassembly. pH-responsive hydrazone-linked doxorubicin was conjugated to the backbone (UN PG FL) containing folate as a targeting ligand. Cobalt carbonyl complex was used for T 2weighted magnetic resonance imaging (MRI). Electron micrographs of optimized molecule CB DX UN PG (4 kDa) FL in an aqueous system have demonstrated about 50−60 nm-sized uniform micelles. The relaxivity study and the one-dimensional (1D) imaging experiments clearly revealed the effect of the nanotheranostics system on transverse relaxation (T 2 ) of water molecules, which validated the system as a T 2 -weighted MRI contrast agent. The detailed in vitro biological studies validated the targeted delivery and anticancer potential of CB DX UN PG (4 kDa) FL. Combining the data on transverse relaxation, folate mediated uptake, and anticancer activity, the designed molecule will have a significant impact on the development of targeted theranostic.

Coordinately Tethered Iron(III) Fluorescent Nanotheranostic Polymer Ascertaining Cancer Cell Mitochondria Destined Potential Chemotherapy and T1-Weighted MRI Competency

“…Along with the effective and precise mitochondrial delivery of chemotherapeutic agents, the monitoring of their therapeutic efficacy is of great importance. Therefore, polymer-based theranostic nanomedicines draw enormous attention in the field of biomedicines worldwide because of their integrated capability of therapy diagnosis along with other advantages like drug solubility, site-specific biodistribution profile, special geometry, and enhanced permeation and retention (EPR) effect. − Cancer patients need proper diagnosis from time to time for their subsequent therapeutic assessment. MRI provides the anatomical details of the tumor through three-dimensional (3D) tomographic images with a high spatiotemporal resolution without employing high-energy electromagnetic waves or any radioactive agents, as in the case of PET, SPECT, and CT. − This eventually facilitates following dose-estimation and thereby significantly reducing the side effects to a great extent and resisting severe damage to healthy tissues and organs.…”

Gadolinium(III) Coordinated Theranostic Polymer for Proficient Sequential Targeting–Combinational Chemotherapy and T1 Weighted Magnetic Resonance Imaging

“…Theranostic-based polymeric nanomedicine gets considerable attention in biomedical use worldwide due to its integrated capability of therapy and diagnosis. , This dual capability of the theranostic system helps estimate the proper dose of administering drug by monitoring the interested region through imaging, which eventually resists the side effects to a great extent . These nanotheranostics reduce the severe damage of healthy tissue or organ and relieve the pain of the patient because of their capability to monitor therapeutic activity at the cancer site by different imaging techniques. − The perfect combination of drug and imaging agents results in the potential theranostic system for a specific disease. , Magnetic resonance imaging (MRI) is one of the most potent cancer-diagnostic techniques used regularly in clinics. , Timely assessment of therapeutic response for a cancer patient is very important for the next therapy decision; thus, MRI provides the anatomical details by 3D tomographic images of affected tissue with high spatiotemporal resolution without employing ionizing radiation . Magnetic inorganic particles assist the relaxation of water proton .…”

“…25,26 Magnetic resonance imaging (MRI) is one of the most potent cancer-diagnostic techniques used regularly in clinics. 27,28 Timely assessment of therapeutic response for a cancer patient is very important for the next therapy decision; thus, MRI provides the anatomical details by 3D tomographic images of affected tissue with high spatiotemporal resolution without employing ionizing radiation. 29 Magnetic inorganic particles assist the relaxation of water proton.…”

Unique Random-Block Polymer Architecture for Site-Specific Mitochondrial Sequestration-Aided Effective Chemotherapeutic Delivery and Enhanced Fluorocarbon Segmental Mobility-Facilitated 19F Magnetic Resonance Imaging

“…The polymer-based theranostic nanomedicine received immense attention in biomedical due to the integrated capability of therapy and diagnosis and other essential prominences like drug solubility, site-specific biodistribution profile, and enhanced permeation and retention effect. − The hydrophobic fluorocarbon segment in the polymeric tracers leads to aggregation and consequently exhibited a deleterious effect on T 2 relaxation time in the acquired 19 F MRI signal. Therefore, signal amplification for 19 F polymeric tracers becomes one of the critical challenges that can be achieved by enhancing segmental mobility of fluorocarbon and consequent augmentation in T 2 relaxation time …”