In an attempt to circumvent the major pitfalls associated with conventional chemotherapy including drug resistance and off-target toxicity, we have adopted a strategy to simultaneously target both mitochondrial DNA (Mt-DNA) and nuclear DNA (n-DNA) with the aid of a targeted theranostic nanodelivery vehicle (TTNDV). Herein, folic acid-anchored psulfo-calix[4]arene (SC 4 )-capped hollow gold nanoparticles (HGNPs) were meticulously loaded with antineoplastic doxorubicin (Dox) and its mitochondrion-targeted analogue, Mt-Dox, in a pretuned ratio (1:100) for sustained thermoresponsive release of cargo. This therapeutic strategy was enabled to eradicate both n-DNA and Mt-DNA leaving no space to develop drug resistance. The SC 4 -capped HGNPs (HGNPSC 4 ) were experimented for the first time as a photothermal (PTT) agent with 61.6% photothermal conversion efficiency, and they generated tunable localized heat more efficiently than bare HGNPs. Moreover, the cavity of SC 4 facilitated the formation of an inclusion complex with folic acid to target the folate receptor expressing cancer cells and imparted enhanced biocompatibility. The as-synthesized TTNDV was demonstrated to be an ideal substrate for surface-enhanced Raman scattering (SERS) to monitor the molecular-level therapeutic progression in cells and a spheroidal model. A significant reduction in the tumor mass with a marked survival benefit was achieved in syngraft murine models through this synergistic photo-chemotherapy. Collectively, this multifunctional nanoplatform offers a robust approach to treat cancer without any scope of generating Dox resistance and off-target toxicity.

Targeting the intracellular "labile" iron pool is turned as a key modulator for cancer progression since the former is responsible for several pathological processes in tumor cells. Herein, we report a nonfluorescent calix[4]arene based triazole appended molecular probe (PTBC) for redox-specific detection of Fe under physiological condition by UV-vis, FT-IR, H NMR, HR-MS spectroscopies, ITC, and the binding strategy between Calix[4]arene and Fe was modeled by DFT calculations. As a new insight PTBC probe showed significant Raman fingerprint through surface enhanced Raman scattering (SERS) modality revealing the ultrasensitive detection of Fe with a LOD of 2 nM. Interestingly, intracellular "iron pool" has been recognized in human lung adenocarcinoma cells (A549) by the PTBC illustrating the distinct Raman mapping. Finally, PTBC imparted cytotoxicity via reactive oxygen species (ROS) generation in cellular milieu signifies its capability as a theranostic molecular probe.

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