Iron(III) Coordinated Theranostic Polyprodrug with Sequential Receptor-Mitochondria Dual Targeting and T1-Weighted Magnetic Resonance Imaging Potency for Effective and Precise Chemotherapy.

The sequential cancer cell receptor and mitochondria dual-targeting single delivery agent deliver chemotherapeutic drug effectively and precisely at the targeted site has become a promising strategy to enhance the drug efficacy and suppressions of cancer cell drug resistance prominence. Herein, required specialty molecules like a chemotherapeutic drug [camptothecin (CPT)], mitochondriotropic segment (triphenyl phosphonium cation) receptor targeting ligand (biotin), and magnetic resonance imaging (MRI)-contrast agent (iron-complex) were tethered to the polyprodrug, CP TP PG BN Fe, using the ring-opening metathesis polymerization technique for potential chemotherapy and simultaneous MRI-based diagnosis. This amphiphilic polyprodrug spontaneously aggregated into nanospheres and exhibited remarkable T1-weighted MRI proficiency. Detail in vitro cellular studies revealed unambiguous mitochondrial delivery of CPT, which eventually enhanced the chemotherapeutic efficacy of CP TP PG BN Fe. Therefore, MRI-tracking, receptor-mitochondria dual targeting, theranostic polyprodrug, and CP TP PG BN Fe opened the way for effective and precise chemotherapy, which would have the attractive potential for diagnosis and decisive dose determination in clinical implications.

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 elevation of the chemotherapeutic efficacy and attenuation of its side effects on healthy cells and tissues become one of the prime targets for the treatment of cancer. Toward this direction, a sequential receptor and mitochondria dual-targeting strategy was implemented in the DX TP PG BN 19F theranostic polymer that was anchored with the chemotherapeutic agent doxorubicin, receptor-targeting biotin, and mitochondria-targeting triphenylphosphonium cations. The polymer was flourished with a unique 19F magnetic resonance imaging (MRI) tracer that exhibited high segmental mobility and eventually led to prolonged T2 relaxation time. Furthermore, for the sake of amphiphilicity, the DX TP PG BN 19F polymer spontaneously aggregated into nano-sphere with positive zeta potential, where the MRI tracer and biotin embedded at the exterior and displayed site-specific targeting and remarkable 19F MRI capability simultaneously. The mitochondria-targeting competency of the DX TP PG BN 19F theranostic polymer was investigated by comparing the non-mitochondrial-targeting DX PG BN 19F polymer using fluorescence microscopic cell imaging in human cervical, HeLa, and breast MCF-7 carcinoma cell lines. Moreover, cytotoxicity experiments of the aforementioned theranostic polymers clarified the enhancement of the chemotherapeutic efficacy of DX TP PG BN 19F theranostic polymers through effective and precise mitochondrial doxorubicin delivery that forced to follow the apoptotic path.

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

Magnetic resonance imaging-aided real-time diagnosis along with enhanced chemotherapeutic efficacy using a sequential receptor and mitochondria dual-targeting polymer theranostic has become a promising strategy for the effective and precise treatment of cancer. Toward the accomplishment of this goal, chlorambucil (chemotherapeutic agent), biotin (receptor targeting agent), a triphenylphosphonium segment (mitochondriotropic agent), and an iron rhodamine complex (integrated fluorescence-MR imaging agent) were tethered under a single polymer. Owing to the polymer's (RD CH PG BN TP Fe) amphiphilic character, it spontaneously self-assembled into nanospheres, which exhibited a remarkable effect on the relaxation of the water proton. Further, the qualitative estimation of the change in intensity for the water-proton signal reflected its potential as a T1 contrast theranostic polymer. The mitochondria targeting competency of positively charged nanospheres was displayed using fluorescence microscopy in human cervical, HeLa, and breast, MCF-7, carcinoma cell lines. Furthermore, cytotoxicity experiments demonstrated the enhanced anticancer efficacy in both cancer cell lines. Therefore, effective and precise chemotherapy through sequential receptor-mitochondria targeting and integrated fluorescence-MR imaging would have attractive potential for decisive dose-determination by constantly monitoring the subject area of interest.

Efficient Design to Monitor the Site-specific Sustained Release of a Non-Emissive Anticancer Drug.

A pH-responsive smart nanocarrier with significant components was synthesized by conjugating the non-emissive anticancer drug methyl orange and polyethylene glycol derived folate moiety to the backbone of polynorbornene. Complete synthesis procedure and characterization methods of three monomers included in the work: norbornene-derived Chlorambucil (Monomer 1), norbornene grafted with polyethylene glycol, and folic acid (Monomer 2) and norbornene attached methyl orange (Monomer 3) connected to the norbornene backbone through ester linkage were clearly discussed. Finally, the random copolymer CHO PEG FOL METH was synthesized by ring-opening metathesis polymerization (ROMP) using Grubbs' second-generation catalyst. Advanced polymer chromatography (APC) was used to find the final polymer's molecular weight and polydispersity index (PDI). Dynamic light scattering, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were utilized to explore the prodrug's size and morphology. Release experiments of the anticancer drug, Chlorambucil and the coloring agent, methyl orange, were performed at different pH and time. Cell viability assay was carried out for determining the rate of survived cells, followed by the treatment of our final polymer named CHO PEG FOL METH.

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

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 fine-tune the hydrophobic/hydrophilic ratio to optimize its self-assembly. 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 T2-weighted 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 (T2) of water molecules, which validated the system as a T2-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.

Iron(III) Coordinated Polymeric Nanomaterial: A Next-Generation Theranostic Agent for High-Resolution T1-Weighted Magnetic Resonance Imaging and Anticancer Drug Delivery.

Theranostic-based nanomedicine plays a crucial role in the field of cancer therapy. This is due to having the capability to combine both therapy and diagnosis together in a single system. Herein a new class of metal-ligand-based nanocarrier in a norbornene backbone has been designed as a theranostic system. Fe3+-terpyridine complex (Fe-Tpy) has been used here as T1 contrast agent for high-resolution MR imaging, and hydrazone-linked doxorubicin is used for effective pH-responsive delivery. Polyethylene glycol functionalized with a folic acid (peg folate) motif is used to make the entire polymeric system dispersible in water for longer retention and site-specific therapy. All these specialty functional groups are anchored in a single system by using the ring-opening metathesis polymerization (ROMP) technique under the norbornene backbone. Relaxivity study and 1D image experiments have shown the utility of Fe-Tpy complex as an effective T1 contrast agent. In vitro studies are performed to confirm the promising potentiality of the nanocarrier as the efficient nanotheranostic system in prostate cancer.