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.

Human hair keratin (HHK) has been successfully explored as raw materials for three‐dimensional scaffolds for soft tissue regeneration due to its excellent biocompatibility and bioactivity. However, none of the reported HHK based scaffolds is able to replicate the strain‐stiffening capacity of living tissues when responding to large deformations. In the present study, strain‐stiffening property was achieved in scaffolds fabricated from HHK via a synergistic effect of well‐defined, aligned microstructure and chemical crosslinking. Directed ice‐templating method was used to fabricate HHK‐based scaffolds with highly aligned (anisotropic) microstructure while oxidized dopamine (ODA) was used to crosslink covalently to HHKs. The resultant HHK‐ODA scaffolds exhibited strain‐stiffening behavior characterized by the increased gradient of the stress–strain curve after the yield point. Both ultimate tensile strength and the elongation at break were enhanced significantly (~700 kPa, ~170%) in comparison to that of HHK scaffolds lacking of aligned microstructure or ODA crosslinking. In vitro cell culture studies indicated that HHK‐ODA scaffolds successfully supported human dermal fibroblasts (HDFs) adhesion, spreading and proliferation. Moreover, anisotropic HHK‐ODA scaffolds guided cell growth in alignment with the defined microstructure as shown by the highly organized cytoskeletal networks and nuclei distribution. The findings suggest that HHK‐ODA scaffolds, with strain‐stiffening properties, biocompatibility and bioactivity, have the potential to be applied as biomimetic matrices for soft tissue regeneration.

Two-dimensional (2D) nanomaterials (NM) have emerged as promising platforms for antibacterial applications. However, the inherent “flatness” of 2D NM often limits the loading of antimicrobial components needed for synergistic bactericidal...

Therapeutic efficiencies of novel cancer treatment modalities such as photodynamic therapy (PDT) and chemodynamic therapy (CDT) are largely diminished in clinical situations due to the disease's constantly evolving nature and harsh conditions of the tumour microenvironment (TME); such as insufficiently low intertumoural pH (pH: < 5) and hydrogen peroxide (H 2 O 2 ) levels. The development of reactive oxygen species (ROS) generating nanomedicine relieves the aforementioned pain points by elevating intertumoural H 2 O 2 levels, typically either via external stimulation (e.g., infrared radiation or ultrasound) or from the innate TME. Their ability to elevate intertumoural H 2 O 2 levels allows them to function as either a standalone anticancer nanomedicine or an adjuvant for follow-up PDT/CDT treatments. L-phenylalanine functionalized nanoscopic porous amino acid mimics (Nano-pPAAMs) stands out amongst the emerging plethora of ROSgenerating nanomaterials for their cancer selectivity and intrinsic ability to generate ROS without external stimulation. However, significant high dosages of Nano-pPAAM are required to effectively eradicate the tumour in both in vitro and in vivo studies.In this study, to reduce the Nano-pPAAM dosage required to eradicate malignancies, two cytotoxins, cetyltrimethylammonium bromide (CTAB) and hydrogen peroxide (H 2 O 2 ), were successfully loaded into the mesoporous silica nanoparticle cores. The improved Nano-pPAAMs were characterized for their particle stability, size, loading content, chemical integrity and were shown to have successfully been able to retain their cytotoxic payload. A total of six cell lines, three cancerous and three healthy cell lines were selected to evaluate the cancer selectiveness and anticancer potency of the loaded Nano-pPAAM.Based on the dose-response curves plotted, the nanoparticles in order of potency, are: Nano-pPAAM (least potent) < H 2 O 2 @pPAAM < CTAB@pPAAM (most potent). Despite the promising results obtained, additional improvements in the Nano-pPAAM design are still recommended to be performed to ensure that the improved Nano-pPAAMs are still selective towards cancer cells. Lay Summary i RONS Reactive Oxygen and Nitrogen Species TEM Transmission Electron Microscopy TME Tumour Microenvironment xiv Treatment Methods Advantages Disadvantages Sources Surgery Fastest cancer treatment method.Potentially able to remove all cancer cells in a localized region.Reduction of mass effect.Unable to treat metastasized cancer.Reoccurrence if cancer is not completely removed post-surgery.Removal of affected tissues may affect patients' quality of life.Surgical complications.