Emerging blood–brain-barrier-crossing nanotechnology for brain cancer theranostics

Tang, Wei; Fan, Wenpei; Lau, Joseph; Deng, Liming; Shen, Zheyu; Chen, Xiaoyuan

doi:10.1039/c8cs00805a

Cited by 409 publications

(301 citation statements)

References 286 publications

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“…[ 5,6 ] Although the tight junctions of BBB at the late stage of brain tumors are disrupted to permit drug penetration into brain, the drug concentration in tumor sites is not sufficient to reach the therapeutic level. [ 7 ] More importantly, the treatment of the early stage of brain tumors is more challenging due to the presence of almost intact BBB. [ 6,8 ] Thus, it is urgent and vital to develop effective delivery systems that efficiently transport therapeutic agents or contrast agents into the CNS for the early treatment and imaging of brain tumors.…”

Section: Introductionmentioning

confidence: 99%

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

Wang

et al. 2020

Adv Funct Materials

144

120

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Glioblastoma multiforme is one of the most fatal intracranial tumors with no effective treatment. The drug concentration in tumor sites is usually insufficient to reach therapeutic levels, due to poor blood–brain‐barrier (BBB) permeability and short biological half‐life. Inspired by the proneness of those malignant tumors to brain metastasis, a brain metastatic tumor cell membrane‐coated nanocarrier with core–shell structure is constructed to cross BBB for imaging and photothermal therapy of early brain tumors. The cell membranes as the shell are extracted from different metastatic tumor cells, which endow the nanoparticles with BBB‐crossing ability and long circulation. Indocyanine green (ICG)‐loaded polymeric nanoparticle as the core allows fluorescence imaging and phototherapy of brain tumors. The as‐prepared biomimetic nanoparticles display superb BBB penetration and effective suppression of tumor growth. These findings suggest the biomimetic nanotechnology provides a new insight for the design of BBB‐crossing nanomaterials and is promising to treat brain diseases.

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Section: Introductionmentioning

confidence: 99%

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

Wang

et al. 2020

Adv Funct Materials

144

120

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“…Finally, we evaluated and discussed the potential of PDLC NPs for future clinical applications. Drug delivery to the brain is hindered by a number of obstacles and the foremost is crossing the blood–brain barrier (BBB) . We first studied the intracellular uptake behavior of PDLC NPs toward PC12 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Drug delivery to the brain is hindered by a number of obstacles and the foremost is crossing the blood-brain barrier (BBB). [59,60] We first studied the intracellular uptake behavior of PDLC NPs toward PC12 cells. The level of PDLC NPs internalized in PC12 cells was quantified by flow cytometry and displayed a concentration-dependent manner ( Figure S15A,B, Supporting Information).…”

Section: Pdlc Nps-mediated Rescue Of Aβ 42 -Induced Cytotoxicitymentioning

confidence: 99%

Engineering Versatile Nanoparticles for Near‐Infrared Light‐Tunable Drug Release and Photothermal Degradation of Amyloid β

Lai

Zhu

et al. 2020

Adv Funct Materials

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Nanomedicines that inhibit/disassemble amyloid β (Aβ) aggregates in Alzheimer's disease (AD) are highly desirable yet remain challenging. Therapeutic efficacy and systemic delivery of reported molecules and nanoparticles (NPs) are hampered by various challenges, including low biocompatibility, off‐target toxicity, and lack of specificity. Herein, a versatile NP is designed by integrating high Aβ‐binding affinity, stimuli‐responsive drug release, and photothermal degradation properties for efficient disassembly of Aβ. Near‐infrared (NIR)‐absorbing conjugated polymer PDPP3T‐O14 serves as a photothermal core while thermal‐responsive polymer 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine at the outer layer as the NIR‐stimuli gatekeeper. Curcumin, an inhibitor of Aβ aggregation, is loaded into the NP with high encapsulation efficiency. The 5‐mer β‐sheet breaker peptides LPFFD (Leu‐Pro‐Phe‐Phe‐Asp) having high binding affinity toward Aβ are further anchored onto the surface of polyethylene glycol‐lipid shell for active Aβ‐targeting. The resultant NPs exhibit good Aβ‐targeting ability and obvious photothermal dissociation effect together with Aβ aggregation‐dependent fluorescence detection capability. Upon NIR laser irradiation, entrapped curcumin can be effectively released from the unconsolidated NPs to enhance the anti‐amyloid activity. In vitro studies demonstrate that the NPs dramatically lower Aβ‐induced cytotoxicity of PC12 cells, and therefore show great potential for the application in AD treatment.

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“…SR‐mediated transcytosis is known as an important route for crossing the BBB . The BBB restricts the passage of approximately 98 % of small molecules (less than 500 Da) and 100 % of macromolecules, which is the major obstacle of brain‐tumor imaging and therapy . The potential of PS‐ b ‐DNA SNA to cross the BBB was explored by constructing an in vitro BBB model (Figure a) and an in vivo evaluation method.…”

Section: Resultsmentioning

confidence: 99%

Organic Spherical Nucleic Acids for the Transport of a NIR‐II‐Emitting Dye Across the Blood–Brain Barrier

et al. 2020

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DNAn anotechnology playsa ni ncreasingly important role in the biomedical field;however,its application in the design of organic nanomaterials is underexplored. Herein, we report the use of DNAnanotechnology to transport aNIR-IIemitting nanofluorophore across the blood-brain barrier (BBB), facilitating non-invasive imaging of brain tumors. Specifically,the DNAblockcopolymer,PS-b-DNA, is synthesized through asolid-phase click reaction. We demonstrate that its self-assembled structure shows exceptional cluster effects, among which BBB-crossing is the most notable.Therefore,PSb-DNAisutilized as an amphiphilic matrix to fabricate aNIR-II nanofluorephore,w hich is applied in in vivo bioimaging. Accordingly,the NIR-II fluorescence signal of the DNA-based nanofluorophore localized at aglioblastoma is 3.8-fold higher than the NIR-II fluorescence signal of the PEG-based counterpart. The notably increased imaging resolution will significantly benefit the further diagnosis and therapyo fb rain tumors.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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Emerging blood–brain-barrier-crossing nanotechnology for brain cancer theranostics

Abstract: The advancements, perspectives, and challenges in blood–brain-barrier (BBB)-crossing nanotechnology for effective brain tumor delivery and highly efficient brain cancer theranostics.

Cited by 409 publications

References 286 publications

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

Engineering Versatile Nanoparticles for Near‐Infrared Light‐Tunable Drug Release and Photothermal Degradation of Amyloid β

Organic Spherical Nucleic Acids for the Transport of a NIR‐II‐Emitting Dye Across the Blood–Brain Barrier

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