4.8 Article

Topical instillation of cell-penetrating peptide-conjugated melphalan blocks metastases of retinoblastoma

期刊

BIOMATERIALS
卷 284, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121493

关键词

Retinoblastoma; Melphalan; Cell-penetrating peptide; Brain metastases; Eye drops

资金

  1. Shanghai Science and Technology Program [21ZR1407100, 21S11905300]
  2. National Natural Science Foundation of China [81573358, 81673361, 81690263]
  3. China Postdoctoral Science Foundation [2020TQ0081]
  4. Development Project of Shanghai Peak Disciplines-Integrative Medicine [20180101]

向作者/读者索取更多资源

This study achieved effective tumor inhibition and prevention of metastases through topical instillation by conjugating a cell-penetrating peptide, 89WP, with melphalan. The conjugated melphalan and other small molecules were absorbed by the eye via a non-corneal pathway, resulting in a prolonged residence duration in the retina.
Retinoblastoma is the most common primary intraocular malignancy in infancy with a metastases-related death risk. However, a safe and convenient treatment without enucleation is still an unmet clinical need. In this work, a cell-penetrating peptide, 89WP, was conjugated with melphalan (89WP-Mel), which achieved high tumor in-hibition effects as intravitreally injected melphalan via topical instillation for the first time. Notably, the outside-in diffusion of instilled 89WP-Mel created a protective shield surrounding the eye, efficiently pre -venting tumor metastases, while the mice treated with intravitreally injected melphalan suffered more brain metastases related death. The ocular absorption of 89WP-conjugated melphalan and other small molecules, both hydrophobic and hydrophilic, occurred via non-corneal pathway with high safety and a prolonged residence duration in retina up to 24 h. The present work paves a new avenue for simultaneous intraocular tumor inhi-bition and extraocular metastases prevention in a safe and convenient way via topical instillation.

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