▎ 摘　　要

Every tumor microenvironment, consequential biological barriers naturally embattle for nanotherapeutics penetration. Disintegrating those obstacles, finding a narrow physiochemical slit with the eye-opening prospect in the way of extravasation or penetration of nanoplatform sounds inevitable. For this reason, our tools comprised of the incorporation of multiple modalities as well as bio-, chemo-functionalization which prompt graphene-based material to release drug, at tumor site adequately with the matching features of these barriers. Those obstacles are being brought with relevant discussions and at rest effective and innovative stimuli design against them have been disputed. Although there has not been reported one regitration of graphene-based material clinical application in terms of drug delivery application; graphene-related reports just have been hampered at the preclinical animal level. This review glimpses the mechanism of cellular internalization of graphene-based material and harnesses its inherent physicochemical properties through current stimuli responsive strategies. Overall, issues covered here deal with the mechanism of internalization, stimuli, nano therapeutics release mechanism, a consequence of increased ionic strength, phenomena of synergistic electroosmosis, cataphoresis; pi pi interaction role, drug's aromatic part contribution, H-bond, Van der Waals force, steric hindrance, electrostatic features, and relevant in-silico calculation outcomes. In this review, graphenebased material drug delivery systems struggling against tumor microenvironment complications and already have been fragmented to realize how microenvironment-based strategies promoted nanotherapeutics penetration through biological barriers. The latest finding on chemical progress in terms of chirality and biodegradability in conjugation with advanced emerging technologies in drug screening have been drawn-out within the probable prospects paradigm.