Biomimetic nanoparticles with enhanced rapamycin delivery for autism spectrum disorder treatment via autophagy activation and oxidative stress modulation.

Miao C, Shen Y, Lang Y, Li H, Gong Y, Liu Y, Li H, Jones BC, Chen F, Feng S

Theranostics15 Jul 2024Cited by 19 (Europe PMC)

PMID39113803PMCIDPMC11303075DOI10.7150/thno.95614PepBankPUB-39113803

Summary

Rationale: Autism spectrum disorder (ASD) represents a complex neurodevelopmental condition lacking specific pharmacological interventions. Given the multifaced etiology of ASD, there exist no effective treatment for ASD. Rapamycin (RAPA) can activate autophagy by inhibiting the mTOR pathway and has exhibited promising effects in treating central nervous system disorders; however, its limited ability to cross the blood-brain barrier (BBB) has hindered its clinical efficacy, leading to substantial side effects. Methods: To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism. Results: The fabricated SCM@RAPA nanoparticles, with an average diameter of 110 nm, exhibit rapid release of RAPA in a pathological environment characterized by oxidative stress. In vitro results demonstrate that SCM@RAPA effectively activate cellular autophagy, reduce intracellular ROS levels, improve mitochondrial function, thereby ameliorating neuronal damage. SS31 peptide modification significantly enhances the BBB penetration and rapid brain accumulation of SCM@RAPA. Notably, SCM@RAPA nanoparticles demonstrate the potential to ameliorate social deficits, improve cognitive function, and reverse neuronal impairments in valproic acid (VPA)-induced ASD models. Conclusions: The therapeutic potential of SCM@RAPA in managing ASD signifies a paradigm shift in autism drug treatment, holding promise for clinical interventions in diverse neurological conditions.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone10

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

01AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Pharmacokinetics
SS31 modification significantly increased blood-brain barrier penetration of the rapamycin nanoparticles.
In plain wordsSS31 modification helped the rapamycin nanoparticles cross the blood-brain barrier better, according to the study.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseBlood-brain barrier penetration of SCM@RAPA
Study
n: not reported in source
Comparator
Nanoparticles without SS31
Outcome group
Pharmacokinetics · Nervous system and cognition
Source sentences
Summary
SS31 peptide modification significantly enhances the BBB penetration
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380306
02AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Pharmacokinetics
SS31 modification significantly increased rapid brain accumulation of the rapamycin nanoparticles.
In plain wordsSS31 modification helped the rapamycin nanoparticles build up faster in the brain, according to the study.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseBrain accumulation of SCM@RAPA
Study
n: not reported in source
Comparator
Nanoparticles without SS31
Outcome group
Pharmacokinetics · Nervous system and cognition
Source sentences
Summary
SS31 peptide modification significantly enhances the BBB penetration and rapid brain accumulation of SCM@RAPA.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380307
03AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In valproic acid-induced autism models, SCM@RAPA nanoparticles ameliorated social deficits.
In plain wordsIn animal autism models, the SS31-modified rapamycin nanoparticles reduced social deficits.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseSocial deficits
Study
n: not reported in source
Valproic acid-induced ASD model
Outcome group
Anxiety and mood · Nervous system and cognition
Source sentences
Summary
Notably, SCM@RAPA nanoparticles demonstrate the potential to ameliorate social deficits, improve cognitive function, and reverse neuronal impairments in valproic acid (VPA)-induced ASD models.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380308
04AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In valproic acid-induced autism models, SCM@RAPA nanoparticles improved cognitive function.
In plain wordsIn animal autism models, the SS31-modified rapamycin nanoparticles improved cognitive function.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseCognitive function
Study
n: not reported in source
Valproic acid-induced ASD model
Outcome group
Cognition and memory · Nervous system and cognition
Source sentences
Summary
Notably, SCM@RAPA nanoparticles demonstrate the potential to ameliorate social deficits, improve cognitive function, and reverse neuronal impairments in valproic acid (VPA)-induced ASD models.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380309
05AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In valproic acid-induced autism models, SCM@RAPA nanoparticles reversed neuronal impairments.
In plain wordsIn animal autism models, the SS31-modified rapamycin nanoparticles reversed neuronal impairments.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseNeuronal impairments
Study
n: not reported in source
Valproic acid-induced ASD model
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Notably, SCM@RAPA nanoparticles demonstrate the potential to ameliorate social deficits, improve cognitive function, and reverse neuronal impairments in valproic acid (VPA)-induced ASD models.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380310
06LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Mechanism
In vitro, SS31-modified nanoparticles carrying rapamycin (SCM@RAPA) activated cellular autophagy.
In plain wordsIn cells, the SS31-modified rapamycin nanoparticles switched on autophagy, the cell's recycling process.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseCellular autophagy
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
In vitro results demonstrate that SCM@RAPA effectively activate cellular autophagy, reduce intracellular ROS levels, improve mitochondrial function, thereby ameliorating neuronal damage.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380302
07LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Mechanism
In vitro, SCM@RAPA reduced intracellular reactive oxygen species levels.
In plain wordsIn cells, the SS31-modified rapamycin nanoparticles lowered levels of reactive oxygen species.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIntracellular ROS
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
In vitro results demonstrate that SCM@RAPA effectively activate cellular autophagy, reduce intracellular ROS levels, improve mitochondrial function, thereby ameliorating neuronal damage.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380303
08LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Mechanism
In vitro, SCM@RAPA improved mitochondrial function.
In plain wordsIn cells, the SS31-modified rapamycin nanoparticles improved mitochondrial function.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial function
Study
n: not reported in source
Outcome group
Mitochondrial function · Nervous system and cognition
Source sentences
Summary
In vitro results demonstrate that SCM@RAPA effectively activate cellular autophagy, reduce intracellular ROS levels, improve mitochondrial function, thereby ameliorating neuronal damage.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380304
09LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Efficacy outcome
In vitro, SCM@RAPA ameliorated neuronal damage.
In plain wordsIn cells, the SS31-modified rapamycin nanoparticles reduced neuronal damage.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseNeuronal damage
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
In vitro results demonstrate that SCM@RAPA effectively activate cellular autophagy, reduce intracellular ROS levels, improve mitochondrial function, thereby ameliorating neuronal damage.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380305
10LabNot a test of Elamipretide (SS-31) aloneIn vitro (cell-free)Other
SS31-modified red blood cell membrane nanoparticles carrying rapamycin (SCM@RAPA, 110 nm) released rapamycin rapidly in an oxidative-stress environment.
In plain wordsIn lab tests, the nanoparticles with rapamycin released the drug quickly in conditions that mimic oxidative stress.
Peptide
Elamipretide (SS-31)
Outcome
Not applicableRAPA release in oxidative environment
Study
n: not reported in source
SCM@RAPA nanoparticles
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Average diameter
110 nm
SCM@RAPA nanoparticles
Source sentences
Summary
The fabricated SCM@RAPA nanoparticles, with an average diameter of 110 nm, exhibit rapid release of RAPA in a pathological environment characterized by oxidative stress.
1 context sentence(design, population, supporting numbers)
Summary · context
To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3911380301

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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