A Nanomedicine Structure–Activity Framework for Research, Development, and Regulation of Future Cancer Therapies

Abstract

Despite their clinical success in drug delivery applications, the potential of theranostic nanomedicines is hampered by mechanistic uncertainty and a lack of scienceinformed regulatory guidance. Both the therapeutic efficacy and the toxicity of nanoformulations are tightly controlled by the complex interplay of the nanoparticle's physicochemical properties and the individual patient/tumor biology; however, it can be difficult to correlate such information with observed outcomes. Additionally, as nanomedicine research attempts to gradually move away from large-scale animal testing, the need for computer-assisted solutions for evaluation will increase. Such models will depend on a clear understanding of structure− activity relationships. This review provides a comprehensive overview of the field of cancer nanomedicine and provides a knowledge framework and foundational interaction maps that can facilitate future research, assessments, and regulation. By forming three complementary maps profiling nanobio interactions and pathways at different levels of biological complexity, a clear picture of a nanoparticle's journey through the body and the therapeutic and adverse consequences of each potential interaction are presented.

Enhancing Skin Cancer Immunotheranostics and Precision Medicine through Functionalized Nanomodulators and Nanosensors: Recent Development and Prospects

“…Studies have indicated that surface modification that modifies the surface to a neutral or anionic state can reduce the toxicity index of PAMAM dendrimers. Studies have shown the toxic effects of dendrimer spanning aggregation of many blood proteins and ROS generation leading to DNA damage [ 136 ]. Generation-5 PAMAM dendrimer, when administered through the intranasal route, can lead to acute lung failure [ 137 ].…”

A Laser Synthesis Route to Boron‐Doped Gold Nanoparticles Designed for X‐Ray Radiotherapy and Boron Neutron Capture Therapy Assisted by CT Imaging

“…Nanomedicine is bringing several innovations to healthcare through the development of a wide set of nanostructures for clinical treatments and bioanalytical procedures. [1,2] The key advantages of nanostructures are in the better properties and performances compared to conventional medical technologies, but also critically rely upon the superior flexibility for tailoring multiple features toward a specific application, as well as the possibility of introducing multiple functions which are traditionally covered only with diverse compounds. [2][3][4] Hence, the progress of nanomedicine requires the continuous exploration of the multiple possibilities available through the combination of inorganic, organic, and biological nanostructured components aiming to the improvement of medical technologies.…”

“…[1,2] The key advantages of nanostructures are in the better properties and performances compared to conventional medical technologies, but also critically rely upon the superior flexibility for tailoring multiple features toward a specific application, as well as the possibility of introducing multiple functions which are traditionally covered only with diverse compounds. [2][3][4] Hence, the progress of nanomedicine requires the continuous exploration of the multiple possibilities available through the combination of inorganic, organic, and biological nanostructured components aiming to the improvement of medical technologies. [1,3,5,6] In this context, nanoalloys are in the spotlight as powerful and versatile materials for the integration of various functionalities in a single nanomedicine.…”

“…[4,19] This is even more advantageous if the nanoparticles are tailored for therapy guidance with well-established tomographic imaging techniques such as MRI, CT, or PET/SPECT. [2,4,[19][20][21][22] For instance, we recently showed that Fe-B NPs combine the radiosensitization ability for boron neutron capture therapy (BNCT) with MRI and interesting magnetic properties for magnetophoretic accumulation in tissues and magnetic hyperthermia. [23] BNCT relies upon the accumulation of a 10 B-rich carrier in the cancer tissues to achieve an advantageous therapeutic index, that is, the ratio of effectiveness to side effects on normal tissues, under irradiation with a low-energy neutron beam.…”

Microfluidic Formulation of Curcumin-Loaded Multiresponsive Gelatin Nanoparticles for Anticancer Therapy

“…In the past three decades, the development of nanotechnology and its application in medicine (nanomedicine) has evolved rapidly. Nanodrug delivery systems (DDSs) have shown strong anticancer effects due to their ability to prevent the degradation of active pharmaceutical ingredients (APIs), being targeted, controlled release, high bioavailability, low toxicity, and side effects. − However, preparing such DDSs is challenging. It is of far-reaching significance to design nanoformulations with stable structures and controllable nanoparticle (NP) sizes .…”