Science Translational Medicine: Cover article: MIT develops engineered particulate-enhanced tumor immunotherapy.

The activation of the interferon gene (STING) signaling stimulator in the tumor microenvironment can produce a powerful anti-tumor response.
Although local dosing of STING astrologists is expected to be used in cancer immunotherapy, in order to achieve efficacy, the drug treatment program requires months of frequent intra-tumor injections, which can lead to poor patient compliance, and multiple intra-tumor injections can also damage the tumor's microencology and vascular networks, thereby increasing the risk of metastasis.
to this, scientists at the Massachusetts Institute of Technology recently developed an engineered particle that releases an excited agent at the right interval with just one injection and shows encouraging results in a variety of cancer mouse models.
the study was published on August 12 as a cover article in the journal Science Translational Medicine, entitled "Engineered PLGA microparticles for long-term, In this study, scientists developed a micro-processed polylactic acid-hydroxyacetic acid (PLGA) particle that can remain at the injection site for long periods of time and release encapsulated STING agonists at a predetermined point in time to simulate multiple injections from days to weeks.
single intra-tumor injection containing STING astrologists can trigger an effective local and systemic anti-tumor immune response, inhibit tumor growth, and prolong survival.
tumor model showed that the tumor metastasis rate was significantly reduced.
study showed that in mouse melanoma models, injections of agonist particles during surgical excision improved the response of immunosupergery blocking therapy and significantly reduced tumor recurrence from 100% to 25%.
, the researchers also demonstrated the therapeutic effect of particles in in-place pancreatic cancer models in mice that could not be injected multiple times.
these findings could directly benefit current STING astration therapy by reducing the number of injections, reducing the risk of metastasis and expanding their applicability to hard-to-reach cancers.
the design and manufacture of a single injection drug delivery platform for cancer immunotherapy using PLGA-MP.
an intra-tumor injection, different PLGA particles reside in the tumor, releasing the encapsulated STING excited agent in pulsed form at discrete points in time and promoting TIL immersion.
diagram of the manufacturing process of the (B) PLGA-MP, which is prepared by filling the target drug into the particle substation and then sealing the substate with the corresponding particle cover by short heating.
scanning electron microscope images of sealed arrays of E(C to E) EP alkalis (C) and particles (D) or individual particles (E).
scales are 500 m (C and D) and 100 m (E).
-resolution X-ray CT representative image of sealed particles encapsulated in 3'3'-cGAMP package(F).
red represents a dry 3'3'-cGAMP.
scale, 100 m.
optical image of an array of sealed particles of glucosaccharies packaged with Alexa Fluor 647.
scale, 1 mm.
preparation researchers used soft photocathing technology to create a cube PLGA particle array with a completely enclosed cavity to load the drugs, which can be filled with water-based or model drugs using a ballast dispenser.
researchers injected PLGA-1, PLGA-2, and PLGA-3 under the skin of AF647-lysal load into hairless mice, and release dynamics studies showed that the particle released AF647-glucosaccharides in the body at a similar time as in vitro.
PLGA-1, PLGA-2 and PLGA-3 have an average release time of 3.9 to 1.1, 8.1 to 1.5 and 11.5 to 1.4 days, respectively.
, the team assessed the effects of different tumor micro-environments (TME) on release dynamics.
data show that PLGA-MP completed the release of the drug at the tumor site at the expected point in time.
verification during the validation phase, the researchers confirmed that a single injection loaded with cGAMP particles (MPs) can effectively inhibit tumor growth, strengthen anti-tumor immunity, and even trigger a powerful systemic anti-tumor immunity.
further tested the therapeutic effect of cGAMP-MPs on the allogeneic transplantation model (KPC model) for pancreatic cancer.
, cGAMP-MPs significantly inhibited primary tumor growth and metastasis to the lungs in the pancreas compared to the untreated group.
, studies have shown that cGAMP-MPs can be used on hard-to-reach tumors.
toxicity analysis PLGA is used in many FDA-approved medical devices due to its biodegradability and biosynorptibility.
cytometer analysis showed that the empty PLGA-MP given in the tumor would not induce any detectable in-place inflammation.
, no weight loss or behavioral changes were observed in mice throughout the treatment period for all in vivo studies.
the 30th day, no particles remaining in the mice were observed, indicating that they had been completely degraded and removed.
, these data show that PLGA-MP does not show toxicity and can be completely degraded and removed in the body.
the efficacy and safety of PLGA-MP is encouraging, there are several areas that can be optimized before clinical transformation.
can increase the load of PLGA-MP.
solution to increasing drug load is to reduce the thickness of the particle wall while maintaining the external dimensions.
, for example, reducing the wall thickness from 100 m to 50 m will increase the drug load by 450%.
addition, the size and geometry of the PLGA-MP can also be optimized to further increase drug load and allow injections with smaller needles.
In summary, by engineering PLGA into a particle structure, the study developed a fully biodegradable delivery system for STING astrologists that avoids repeated injections and visits, reduces the risk of tumor metastasis, and ultimately improves patient compliance and reduces financial costs, helping to improve the effectiveness of cancer immunotherapy based on STING astrologists.
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