Rational nanocarrier design towards clinical translation of cancer nanotherapy

Abstract

The past decades have witnessed an exponential growth in research of cancer nanomedicine, which has evolved into an interdisciplinary field involving chemistry, physics, biology, and pharmacology, pathophysiology, immunology and clinical science in cancer research and treatment. The application of nanoparticles in drug delivery increases the solubility and decreases the toxicity of free drug molecules. The unique feature of cancer pathophysiology, e.g. leaky blood vessel, presents a unique opportunity for nanocarriers to deliver therapeutics selectively to tumor sites based on size selectivity. However, the clinical translation of nanomedicine is mostly limited to the classical liposomal formulations and PEGylation of therapeutics. Numbers of reasons hinder the clinical translation of the novel nanoparticles developed in the last decades for drug delivery. Comprehensive understanding of the properties of nanocarriers and their interactions with the physiological and pathological interfaces is critical to design effective nanoformulations. In addition, understanding the general principles and concerns in pharmaceutical industries and clinical practice for nanotherapeutic development is essential to develop a translatable nanoformulations via rational nanocarrier designs. In this account, we will review the relationship between the physiochemical properties of nanocarriers and biodistribution, and interactions with biological and immunological systems for effective drug delivery and cancer treatments. Further, we review the strategies for rational design of nanocarriers via structure-based approach and bio-mimicking systems to facilitate the clinical translation in enhancing cancer treatment via both chemotherapy and immunotherapy.

Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders

“…It is arguable that with more widespread adoption of in vitro modelling platforms for conducting transport and biocompatability studies, this number is set to increase [14]. At present, considerable precedence is given to their application in cancer nanotherapy [9,16] as this is arguably the most ubiquitous indication for most rationally designed nanoplatforms. A snapshot of the of privately and publicly funded clinical studies conducted around the world is given in Table 3 (www.clinicaltrials.gov accessed on 19/09/21).…”

“…A snapshot of the of privately and publicly funded clinical studies conducted around the world is given in Table 3 (www.clinicaltrials.gov accessed on 19/09/21). In terms of rational design of nanotheranostic platforms, a number of key characteristics and design principles [16] should be considered from the outset in order to maximise the probabilistic outcomes of: (1) transport across the BBB, (2) biocompatibility and (3) measurable concentrations that are therapeutically useful. In essence, the fundamental goal for a formulation scientist is to design a nanotheranostic platform that uniformly crosses the BBB in a predictive and reproducible way, localises in the target regions and tissues of the brain or associated tumour/embolism and elicits a therapeutic effect (ideally with a sustained release profile) without causing significant accumulation or adverse effects.…”

“…Polymeric and metallic nanoplatforms constitute the most pervasive in the field for development of novel neuropharmaceuticals [16] due to the comparative lack of biomaterial-based studies. While numerous candidates, as alluded to earlier, have shown promise preclinically in vitro, and in some settings have reached phase 2 trials, the vast number of discontinued or unproven designs are a direct consequence of the "trial and error" philosophy [219], which has hampered research to date.…”

“…The nanotheranostic platforms (NTPs) can generally be stratified on the basis of their constituent composition into organic, inorganic, metallic or carbon, but also sometimes more usefully grouped by their properties, and as such comprise the metallic, magnetic and semi-conducting NTPs. [15] This latter classification strategy is more useful in terms of providing an orthogonal comparison of such multifunctional carriers consisting of a core matrix, a diagnostic agent, a therapeutic agent and a tuneable surface of targeting moieties and polymeric coating for colloidal stability and conjugatable functional groups [16]. As these structures are typically in the range of 1 to 100 nm, they exhibit unique properties such as high surface area to volume ratio, enhanced permeability and retention, electrical and optical properties that do not apply at the macromolecular level [17].…”

Photoacoustic Properties of Polypyrrole Nanoparticles

“…In comparison with low-molecular dyes they broaden imaging ways due to their different biodistribution. In particular, nanoparticles leak significantly less into the interstitium; the signal loss is caused by organ or cell functions rather than plain diffusion, and nanoparticles can be better targeted to tissues or cells [ 14 , 15 , 16 , 17 ]. Particles based on noble metals usually reach absorption levels several orders of magnitude greater than traditional dyes, depending on their size, shape or surface [ 18 ].…”