. Author manuscript; available in PMC: 2023 Dec 1.

Published in final edited form as: Adv Drug Deliv Rev. 2022 Nov 11;191:114619. doi: 10.1016/j.addr.2022.114619

Table 3.

Pros and cons of different BBB crossing/disturbing strategies

Strategies	Methodology	Pros	Cons
Passive targeting	/	Simple structure of nanoparticle; High specificity (lesion dependent distribution); safety	Heterogeneous distribution; low distribution; brain tumor type and stage dependent
Biological interfacial interaction	Receptor/Transporter-mediated transcytosis	Receptor/transporter mediated high efficiency and relative high distribution; Active targeting and multiple targeting mediated highly specific distribution in brain tumor	Relative complicated and high-cost nanoparticles; Off-target distribution deriving from non-exclusive distribution of receptor/transporter; Compromised target ability due to the competition from endogenous ligand and the formation of protein corona
Physicochemical interaction	Adsorptive mediated transcytosis	High transcytosis efficacy; High distribution in brain tumor;	No-specific high distribution in brain; limited tissue selectivity; Potential system toxicity
Physicochemical interaction	Temporary BBB opening and disrupting	Highly efficient, enables focus on targeted region; temporary and reversible BBB opening; most method approved in the clinic;	Potential side effects, such as increased intracranial pressure, chronic inflammation; Non-specific opening of the BBB;
Living cell	/	High specificity; High efficiency; High carry capacity; Decreased drug immunogenicity	Complicated operation; High cost; Heterogeneous outcome; Potential system toxicity; Poor spatial and temporal control of cargoes release