“…Moreover, tailoring the physicochemical properties of nanoparticles, such as morphology (geometry and shape), size, surface charge, surface chemistry, composition, hydrophobicity, porosity, roughness, rigidity and colloidal stability can influence the series of biological processes that in turn determine the overall therapeutic efficacy of cancer nanomedicines ( Figure 2). [22,75,76] Thus, in order to utilize the potential of these advanced multifunctional, stimuli-responsive and theranostic nanoparticles that are showing promising therapeutic advantages at the preclinical stages in order to accelerate their clinical translation, from the nanoparticle engineering prospects focus should be at the practical challenges in the design, development of advanced targeted nanoparticle engineering, which include: (i) optimization of the preparation of complex nanoparticle designs using simple steps without the requirement of multi-step processes; (ii) full characterization of the main physicochemical properties of the nanoparticles using quantitative analytical methods and ensure the quality of the nanoparticle characterization; (iii) optimization of the loading and release of payloads and assessment of the potential cross reactions in case of combination of payloads; (iv) utilization of controllable, site specific, robust and reproducible bioconjugation chemistries for attaching targeting ligands on the surface of the nanoparticles; (v) optimization of the bio-physicochemical properties of the nanoparticles to achieve long half-life in blood circulation, favourable biodistribution and pharmacokinetics, differential accumulation in target tissue; (vi) development of scalable manufacturing processes that can adopted to large scale production.…”