Emerging resistance to all available antibiotics highlights the need to develop new antibiotics with novel mechanisms of action. Most of the currently used antibiotics target Gram-positive bacteria while Gram-negative bacteria easily bypass the action of most drug molecules because of their unique outer membrane. This additional layer acts as a potent barrier restricting the entry of compounds into the cell. In this scenario, several approaches have been elucidated to increase the accumulation of compounds into Gram-negative bacteria. This review includes a brief description of the physicochemical properties that can aid compounds to enter and accumulate in Gram-negative bacteria and covers different strategies to target or bypass the outer membrane-mediated barrier in Gram-negative bacterial pathogens.

A photoactivatable dopamine-conjugated platinum(IV) anticancer complex (Pt-DA) has been incorporated into G-quadruplex G₄K⁺ borate hydrogels by using borate ester linkages (Pt-G₄K⁺B hydrogel). These were characterized by ¹¹B NMR, attenuated total reflection Fourier transform infrared spectroscopy, circular dichroism, scanning electron microscopy and transmission electron microscopy. Microscopy investigations revealed the transformation of an extended fiber assembly into discrete flakes after incorporation of Pt-DA. Pt-DA showed photocytotoxicity against cisplatin-resistant A2780Cis human ovarian cancer cells (IC₅₀ 74 μM, blue light) with a photocytotoxic index <2, whereas Pt-G₄K⁺B hydrogels exhibited more potent photocytotoxicity (IC₅₀ 3 μM, blue light) with a photocytotoxic index >5. Most notably, Pt-DA and Pt-G₄K⁺B hydrogels show selective phototoxicity for cancer cells versus normal fibroblast cells (MRC5).

We report facile one-pot synthesis of water-soluble green fluorescent gold nanoclusters (AuNCs), capped with 8-mercapto-9-propyladenine. The synthesized AuNCs were characterized by Fourier transform infrared (FTIR), powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), ¹H NMR, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. These nanoclusters show high photostability and biocompatibility. We observed that AuNCs stain cell nuclei with high specificity, where the mechanism of AuNC uptake was established through pathway-specific uptake inhibitors. These studies revealed that cell internalization of AuNCs occurs via a macropinocytosis pathway.