Potent‐By‐Design: Amino Acids Mimicking Porous Nanotherapeutics with Intrinsic Anticancer Targeting Properties

Abstract

Exogenous sources of amino acids are essential nutrients to fuel cancer growth. Here, the increased demand for amino acid displayed by cancer cells is unconventionally exploited as a design principle to replete cancer cells with apoptosis inducing nanoscopic porous amino acid mimics (Nano‐PAAM). A small library consisting of nine essential amino acids nanoconjugates (30 nm) are synthesized, and the in vitro anticancer activity is evaluated. Among the Nano‐PAAMs, l‐phenylalanine functionalized Nano‐PAAM (Nano‐pPAAM) has emerged as a novel nanotherapeutics with excellent intrinsic anticancer and cancer‐selective properties. The therapeutic efficacy of Nano‐pPAAM against a panel of human breast, gastric, and skin cancer cells could be ascribed to the specific targeting of the overexpressed human large neutral amino acid transporter SLC7A5 (LAT‐1) in cancer cells, and its intracellular reactive oxygen species (ROS) inducing properties of the nanoporous core. At the mechanistic level, it is revealed that Nano‐pPAAM could activate both the extrinsic and intrinsic apoptosis pathways to exert a potent “double‐whammy” anticancer effect. The potential clinical utility of Nano‐pPAAM is further investigated using an MDA‐MB‐231 xenograft in NOD scid gamma mice, where an overall suppression of tumor growth by 60% is achieved without the aid of any drugs or application of external stimuli.

Direct and Label‐Free Cell Status Monitoring of Spheroids and Microcarriers Using Microfluidic Impedance Cytometry

“…[10] Typically, cellular aggregates are dissociated into single cells and stained to determine viability as endpoint measurements. [11,12] Electrical impedance spectroscopy is a label-free approach for characterization of material dielectric properties in a static (non-flow) manner, [13] and has been recently applied in microfluidic systems to monitor 3D 3D cellular spheroids/microcarriers (100 µm-1 mm) are widely used in biomanufacturing, and non-invasive biosensors are useful to monitor cell quality in bioprocesses. In this work, a novel microfluidic approach for label-free and continuous-flow monitoring of single spheroid/microcarrier (hydrogel and Cytodex) based on electrical impedance spectroscopy using co-planar Field's metal electrodes is reported.…”

Pharmacologic approaches to amino acid depletion for cancer therapy

“…301 Of course, strategies targeting tumor amino acid metabolism are not limited to amino acid depletion and uptake blockage. Recently, Wu et al 302 effects. 302 This strategy exhibited the potential for developing nanoparticle-centric approaches for targeting amino acid dependency in cancer cells.…”

“…Recently, Wu et al 302 effects. 302 This strategy exhibited the potential for developing nanoparticle-centric approaches for targeting amino acid dependency in cancer cells. Although not reviewed here, it is worth mentioning that targeting key enzymes in amino acid metabolic pathways is another commonly explored approach.…”

Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy

“…In the search for suitable drugs, it was reported that amino acids mimicking nanotherapeutics could exhibit intrinsic anticancer targeting properties for skin cancer treatment. L-phenylalanine functionalized MSNs, for example, have achieved an overall suppression of tumor growth by 60% without the aid of any external stimuli or drugs [ 134 ]. Verteporfin-loaded MSNs could also inhibit the in vitro and in vivo proliferation of mouse melanoma by reducing the tumor mass of 50.2 ± 6.6% compared to the untreated (only glycerol) mice [ 135 ].…”