Tuning the Organ Tropism of Polymersome for Spleen‐Selective Nanovaccine Delivery to Boost Cancer Immunotherapy

Abstract

The past few decades have witnessed explosive development in drug delivery systems. However, in vivo delivery suffers from non‐specific distribution in non‐targeted organs or tissues, which may cause undesired side effects and even genotoxicity. Here, a general strategy that enables tuning the tropism of polymersomes for liver‐ and spleen‐selective delivery is reported. By using a library screening approach, spleen‐targeted polymersome PH9‐Aln‐8020 and liver‐targeted polymersome PA9‐ZP3‐5050 are identified accordingly. Meanwhile, the second near‐infrared (NIR‐II) fluorescence imaging allows for in vivo dynamic evaluation of their spatial and temporal accumulation in specific tissues. O ur findings indicate that both polymer composition and protein corona on the surface are essential to determine the in vivo fate of polymersomes and tendency for specific organs. Importantly, PH9‐Aln‐8020 is employed as a systemic nanocarrier to co‐deliver the antigen and adjuvant, which remarkably boost splenic immune responses in acute myeloid leukemia, melanoma, and melanoma lung metastasis mouse models. This study may open a new frontier for polymersomes in organ‐selective delivery and other biomedical applications.

Advances in non-viral mRNA delivery to the spleen

“…Gu et al synthesized a histidine-conjugated PLGA PEG diblock copolymer and formulated this polymer alongside either a zwitterionic or bisphosphonate helper polymer for mRNA delivery. 153 It was found addition of the bisphosphonate helper polymer rather than the zwitterionic polymer dictated spleen tropism, and it was hypothesized the reason for differences in tropism was dictated by the protein corona formation on the polymer. Delivery of this polymer to the spleen enabled for effective delivery of mRNA-encoded antigens to dendritic cells within the spleen resulting in the activation of CD8+ T Cells.…”

“…Delivery of this polymer to the spleen enabled for effective delivery of mRNA-encoded antigens to dendritic cells within the spleen resulting in the activation of CD8+ T Cells. 153…”

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

“…Immunogenic cell death (ICD), a promising approach in anticancer immunotherapy, has garnered significant attention for its potential to elicit enduring antitumor immune responses, thereby preventing cancer recurrence and metastasis. − Hence, continuous efforts are directed toward developing innovative ICD inducers, particularly in the realms of chemotherapy and phototherapy, for immunotherapy against solid tumors. − Despite some pioneering examples, practical hurdles remain for the widespread application of established ICD inducers in immunotherapy. − On the one hand, the effectiveness of ICD-inducing immune responses is intricately linked to the production of reactive oxygen species (ROS). However, many ICD inducers struggle to generate sufficient intracellular ROS due to their intrinsic characteristics or a lack of organelle targeting ability, resulting in a low rate of immune responsiveness. − Furthermore, considering the limited diffusion radius (<0.02 μm) and the short lifespan (<0.04 μs) of ROS, most existing ICD inducers with unsatisfactory penetration and retention performance exhibit seriously compromised ROS generation in deep-seated solid tumors, thereby hindering therapeutic outcomes. − On the other hand, determining the minimal effective dose of an ICD inducer regimen, which maximizes immunological benefits while minimizing side effects, remains a formidable challenge. − For example, several chemotherapy-based ICD inducers (e.g., oxaliplatin) currently evoke ICD at a high dose (∼300 μM), potentially leading to unexpected adverse effects on healthy organs .…”

Polymersomes for Therapeutic Protein and Peptide Delivery: Towards Better Loading Properties

“… 54 Other therapeutic applications, ranging from central nervous system diseases 30 to tissue regeneration, 55 have also been summarized in the above review. Recently, there have been several works on polymersomes loaded with proteins and peptides, with topics including cancer immunotherapy, 32 diffuse large B-cell lymphoma treatment, 33 and dengue vaccine. 34 As for ongoing clinical trial situations, in 2022, ACM Biolabs applied for a Phase I clinical trial of ACM-001, an adjuvanted SARS-CoV-2 spike protein (beta variant) vaccine.…”